Zoo 317 Heredity, Evolution and Society

GLOSSARY

ABO blood groups Red blood cell antigens detected by antibodies that are naturally-occurring (i.e. not produced through artifical immunization). There are three common polymorphic alleles, A, B, and O, with A and Bcodominant to each other and both dominant to O. Persons produce antibodies against the A and B antigens that their red cells do not have but not against O. Thus an AB person produces no antibodies, whereas an OO person produces both anti-A and anti-B antibodies. Mixing blood of persons with different ABO types results in antibodies of one person attacking the corresponding antigens of the other, resulting in agglutination of the cells. In blood transfusions, it is important that the donor and recipient have blood that is compatible. The ABO groups are the most common reason for incompatibility, and the donor and recipient are always matched for ABO types.

achondroplasia A dominantly inherited
form of dwarfism characterized by short limbs but normal trunk. The gene
involved is the fibroblast growth factor receptor-3 gene, located at 4p16.3.
More information is available in
OMIM.

acrocentric [Greek akron extremity
+ centric.] A chromosome in which the centromere
is located near one end, creating very unequal arms.

active immunity The production of antibodies by an individual as a result of immunization, either by infection or vaccination. Active immunity creates memory cells that provide immunity throughout the life of the individual.

adaptation The concept that organisms
become better able to exploit their environment and survive in it over
evolutionary time scales. This process occurs because of natural selection
and involves differential survival and reproduction of better adapted gene
combinations.

adenosine triphosphate Commonly
called ATP, this substance stores energy in the form of chemical
bonds. ATP is produced in mitochondria
(also in chloroplasts in plants) and is used to drive the vast number of
chemical reactions in a cell that require energy. If more ATP is produced
than is required, the excess is stored in the form of fat and glycogen
(or starch in plants).

albinism A condition in which normal pigment
is absent or greatly diminished. Complete absence of pigment in humans
is inherited as an autosomal recessive trait. However, there are additional
forms of albinism with other modes of transmission. See OMIM
for more extensive discussion and links to other forms of albinism.

alkaptonuria A disorder
in the breakdown of the amino acids phenylalanine
and tyrosine. In normal metabolism, phenylalanine
is converted to tyrosine, which is converted in several steps to homogentisic
acid and then into other metabolic endproducts. The enzyme
that catalyzes the breakdown of homogentisic acid (homogentisic acid oxidase)
is coded by a single gene (AKU) on chromosome 3. Persons homozygous
for defective AKU alleles cannot carry out the breakdown of homogentisic
acid, which accummulates in the blood and is then excreted in the urine.
On exposure to air, homogentisic acid spontaneously forms a black pigment,
which is readily recognizable on wet diapers. Alkaptonuria is a relatively
benign disorder, the principal problem being formation of deposits in joints,
leading to a form of arthritis. More extensive information is available
in OMIM.

allele [Greek allelon of one another.]
An alternate form of a gene. Some alleles are wildtype,
i.e. common and normal. Others are rare and may or may not be associated
with normal function. There may be hundreds of alleles for a particular
gene, but usually only one or a few are common.

Alzheimer disease A disease of late onset involving loss of mental function and memory. It is often called senile dementia. "Early onset" cases appear before ages 60-65 years; the great majority of cases are "late onset," appearing in the seventies and eighties. Early onset cases frequently show autosomal dominant inheritance, due to the presence of mutant alleles at any of three loci. The inheritance of late onset cases is less clear and is more likely multifactorial, with genetic predisposition and environmental factors both contributing to the risk. The presence of E4 alleles at the apoliproprotein E locus is an important risk factor for late onset Alzheimer disease. Additional information is available in OMIM.

amino acid An organic compound
that has both an amino group and a carboxyl
group as part of its structure. The type formula is H2–N–CH(R)–COOH,
where the hydrogen (H) and the R group are attached covalently
to the carbon (C) drawn to their left. The R group can be any of dozens
of atomic structures, the simplest being a single H. Amino acids can have
a variety of functions in metabolism, but they
are especially interesting because they are the building blocks of proteins.
They can be joined together in any order by peptide
bonds, and there can exist a vast number of polypeptide chains that
differ in their amino acid sequences.

amino group A functional
group consisting of one nitrogen and two hydrogens: –NH2.
Each H is bound to the N by a single covalent
bond, satisfying the valence requirements of
N for three bonds and H for one. Because the nitrogen has unshared
electrons in its outer shell, it attracts hydrogen ions, which have no
electrons, and forms the structure –NH3+, which has
a positive charge. The ability to bind/neutralize hydrogen ions classifies
the amino group as a base or alkaline group.

aminoacyl tRNA The molecule
that consists of an amino acid bound covalently
through its carboxyl group to its specific
tRNA. These tRNA derivatives are necessary
for translation of the nucleic acid code into
amino acid sequences in proteins.

amniocentesis Collecting
a sample of amniotic fluid, which surrounds
a fetus. The amniotic fluid contains cells that are of fetal origin
and that can be used for genetic studies of the fetus. The optimal
time for collection is about 16 weeks gestation, at which point there is
enough fluid to withdraw a useful sample. The liquid can be analyzed
for various chemical constituents, and the cells can be analyzed directly
by PCR or cultured for chromosome
studies. Amniocentesis is a major procedure used in prenatal
diagnosis.

amniotic fluid The liquid
in which an embryo or fetus is suspended within the amniotic sac.
It consists of both liquid and cells, the latter of fetal origin.
The cells are especially useful for genetic studies.

anaphase [Greek ana back + phase.]
The phase of nuclear division in which newly formed chromosomes are pulled
along the microtubules of the spindle
to the opposite poles. In mitosis, former sister
chromatids, now chromosomes, move to opposite
poles.

anaphylaxis An immediate hyperreactive immune response to an allergen. Symptoms may include respiratory distress and low blood pressure. Without prompt intervention, death may result.

androgen [Greek andros man + gennan produce.] Any male hormone, of which testosterone
is an example. The androgens are steroids and thus are closely related to female hormones (estrogens, progesterone) and to adrenal hormones.

androgen insensitivity [Gene
symbol AIS.] A disorder in which tissues lack functional androgen
receptors and therefore cannot respond to testosterone.
The condition was earlier called testicular feminization. The defect
is in the gene for the androgen receptor
(AR), on the X chromosome. Persons who are 46,XY but who have a
nonfunctioning AR develop female external genitalia and an otherwise
normal female external appearance, described in some cases as voluptuous.
They lack the internal structures associated with Mullerian
duct development (fallopian tubes and uterus) and the vagina is short.
Some do not develop axillary and pubic hair. The intra-abdominal gonads
are testes, with normal male production of testosterone. More information
is available in OMIM.

anencephaly [an negative + Greek enkaphalos brain.] A condition in which the main part of the brain (cerebrum) is missing or greatly diminished.

aneuploid Having a chromosome
complement that is not a multiple of the basic haploid
complement. In humans, aneuploidy usually involves having an extra
chromosome (trisomy) or deficiency of a chromosome
(monosomy).

anion [Pronounced AN-eye-on,
more or less.] A negatively charged atom or molecule. See ion.

antibody A protein produced
by B-cells, specifically by the plasma cells, that binds to a very specific target. Such targets are called antigens and induce the production of the specific antibodies. An individual can produce an enormous number of different antibodies, each specific for its target. The diversity is possible primarily because of the rearrangements of the DNA in a limited number of coding regions, a process that is limited to antibodies and T-cell receptors. An antibody molecule is a tetrameric protein, composed of two identical large polypeptides and two identical small polypeptides. The molecular formula can thus be represented as H2L2. Combinations of different forms of the H and L polypeptides generate the enormous diversity of antibodies.

anthropoid [Greek anthropos man + eidos form.] The "human-like" primates, including monkeys, apes, and, of course, humans. These are grouped into the suborder Anthropoidea. The remaining primates are in the suborder Prosimii.

anticipation The phenomenon
of younger age of appearance of a late onset trait in succeeding generations.
The only known cause of anticipation is trinucleotide
expansion.

anticodon The three nucleotides
on transfer RNA (tRNA) that are complementary
to a codon in messenger RNA
(mRNA). This complementarity binds the tRNA to the mRNA, and the
attached amino acid is then transferred to the nascent polypeptide chain.
This specificity of binding of the anticodons to the mRNA codons accounts
for the fidelity with which a gene is translated into protein.

antigen Any substance that, when introduced into the body of a mammal and many other vertebrates, will induce production of antibodies. Most antigens are proteins, but almost any substance is capable of being antigenic on rare occasions.

anti-Mullerian hormone [Gene
symbol AMH.] A hormone secreted by the Sertoli cells of the seminiferous
tubules in the testes of developing male embryos and fetuses. Previously
called Mullerian-inhibiting hormone/factor/substance. Its function is to
suppress development of the embryonic Mullerian ducts, which form the fallopian
tubes, uterus, and upper third of the vagina in females. For additional
information, see OMIM.

antiparallel Going in
opposite directions, as in two arrows lying parallel but with arrow heads
pointing in opposite directions. The two polynucleotide strands of
DNA have direction, and pairing occurs only if the directions are opposite.
See Watson-Crick.

antisense strand The
DNA strand that serves as the template in transcription.
Also called the template strand.

apolipoprotein E A protein in blood that is usually bound to certain fats. There are three common alleles, one of which, E4, is associated with increased risk of Alzheimer disease. Additional information on apoE can be found in OMIM.

armadillo [Spanish diminutive of armado,
from Latin armatus.] A small nocturnal mammal of the family Dasypodidae, the icon of the Austin area because of its "live and let live" attitude. This derives from its habit of retreating into its hard armor when threatened, though this is scant protection from oncoming cars. Many persons who have
lived in armadillo country for years know them only in the form of road kill. Armadillos are famous in genetics because they produce litters of four monozygotic offspring, a trick not known to occur in any other mammal.

artificial insemination
Introduction of spermatozoa artificially into the uterus rather than by sexual intercourse. This procedure is most often used when the prospective father is infertile, and another male is used as a source of semen.

asexual reproduction Reproduction
in which the products, either cells or organisms, are genetically identical
to the parent. Mitosis is an example of asexual reproduction at the cell
level. See sexual reproduction.

atom The smallest unit of tangible
matter. Atoms are composed of various subatomic particles, of which
electrons, protons, and neutrons
are the most important in understanding the properties of atoms at the
level of biology. Each atom consists of a nucleus composed of protons,
each of which has one positive electrical charge, and neutrons, which are
electrically neutral. Shells of electrons, each with one negative
electrical charge, surround the nucleus. In the unreacted, neutral
state, the number of electrons is equal to the number of protons.
The smallest atom is that of hydrogen, which consists
of one proton in the nucleus, along with zero to two neutrons, and one
electron in the shell. It has an atomic
number of one. Increasing the number of protons changes the characteristics
of the atom, changing it into a different element.

atomic mass The mass of
an atom of a particular element. Often called
atomic weight, though mass is the correct term. One unit of
atomic mass = 1.66 × 10–24 grams = 1 dalton. This
is approximately the mass of one proton or neutron. Electrons have
a much smaller mass and contribute little to the mass of an atom.

atomic nucleus The central
core of an atom. The nucleus consists of protons
and, with the exception of the common form of hydrogen,
neutrons.

atomic number The number
of protons in an atomic
nucleus. Atomic numbers vary from 1 for hydrogen
to 103 for the man-made element Lawrencium.
The chemical properties of an element are a function of the number of protons
in the nucleus, which in turn determine the stable number of electrons
in the surrounding shells.

Australopithecus [Latin australis southern + Greek pithekos ape.] One of two hominid genera, represented entirely by fossil forms, all in east and southest Africa. The earliest species is designated A. anamensis and is represented by limited fossil material dated to ca. 4 million ybp (years before present). Another group of fossils, designated A. afarensis, are from a species that lived from ca. 4 million ybp to 2.5 million ybp. A. africanus arose perhaps as early as 3 million ybp and lasted at least to about 2 million ybp. Two other large groups, A. boisei and A. robustus, arose ca. 2.5 million ybp and lasted until nearly 1 million ybp, well past the formation of the Homo lineage. These two species are sometimes placed in a separate genus, Paranthropus. It is not clear which of these fossil species may have been ancestral to humans, except for the last two who lived too late.

autosomal The adjective form
of autosome.

autosome A chromosome other
than the chromosomes involved in sex determination. Humans have 22 pairs
of autosomes + one pair of sex chromosomes.

B-lymphocyte One of the two major types of lymphocytes, responsible primarily for humoral immunity (antibodies). B-lymphocytes were so-named because they "mature" in chickens in the bursa, a gland that is not present as such in mammals. Maturation appears instead to occur in the bone marrow. When stimulated by antigens, B-lymphocytes, which initially have little cytoplasm, become large plasma cells, which are the cells with active antibody production. Some of the B-lymphocytes also become memory cells, forming a reservoir of cells that are long-lived and that are primed to expand for antibody production in the event of later challenge with the specific antigen.

backcross A cross between
the F1 generation and the presumptive homozygous recessive parental
stock. Such a cross would be Aa × aa and should produce
equal numbers of Aa and aa offspring.

bacteria [Sing. bacterium;
Greek bakterion little stick.] One-cell organisms that lack
nuclei, i.e. they are prokaryotes.
Many of the "germs" that cause disease are bacteria. However, most
are benign. Indeed, we depend on them for many natural processes.
Several have been important experimentally in understanding the structure
of genes and how they function.

bacteriophage [bacterio-
+ phagein to eat.] A virus that attacks
and destroys bacteria. Studies of bacteriophage
were important in early development of the field of molecular biology.

balanced translocation
A translocation in which no genetic materials
are lost. Such translocations are consistent with normal development
and function except for possible interruptions of gene function at translocation
breakpoints.

base A molecule that has the ability
to bind hydrogen ions, H+, thereby neutralizing their acidity. Basic,
in this sense, is synonymous with alkaline. While there are many
basic molecules that are important in biology, those that occur in nucleic
acids merit special note, as they are often referred to collectively
as bases. These are the purinesadenine
and guanine and the pyrimidinescytosine, thymine, and uracil.

base pair A common designation
of the pairs of nucleotides that are complementary
in a DNA double helix. As a matter
of convenience, a DNA sequence is often represented by the sequence of
bases on one strand. It is understood, but frequently not stated,
that each such base represents the nucleotide pair. Thus, in writing
a sequence such as -G-A-C-, the complementary sequence -C-T-G- is understood.
The context of the discussion should make clear whether a single strand
of DNA is inferred or whether the double-stranded structure is the subject.

benign tumor An abnormal growth that does not spread to or invade other tissues. As the name implies, benign tumors generally do not cause problems except for those instances in which large size interferes with function of surrounding tissues. This is especially a problem in benign brain tumors, for example, because of encasement with the skull. Some benign tumors may secrete hormones or other substances that cause physiological problems. A few benign tumors have increased likelihood of progressing to malignant tumors.

binomial nomenclature The system of biological classification developed by Linnaeus (Carl von Linné). In the Linnaean system, the basic unit of classification is the species. Closely related species are grouped into the same genus (pl. genera). In referring to an organism by its scientific name, both the genus and species are given. For example, humans are Homo sapiens, being members of the genus Homo and the species sapiens within that genus. Related genera are grouped into families, which are grouped into orders, which are grouped into classes, which are grouped into phyla (s. phylum), which are grouped into kingdoms. Humans are members of the kingdom Animalia, phylum Chordata, Class Mammalia, Order Primates, family Hominidae, genus Homo, and species sapiens. There are rigid rules in writing these designations: The genus is capitalized; the species is not. Both are italicized, unless you are italics-challenged, in which case they must be underlined. Other levels of organization are capitalized but not italicized.

bipolar affective disorder A psychotic disorder in which there are major mood changes between periods of mania and periods of depression. Also known as manic-depressive psychosis.

blastocyst The early
mammalian embryonic stage in which the mass of cells forms a hollow sphere.
Most of the cells that form the sphere are trophoblasts.
A few are embryoblasts and will form the inner
cell mass.

blood group compatibility The absence of red blood cell antigens and the corresponding antibodies to them in mixtures of blood. The term is also used to describe potential mismatches between mother and fetus, in which the fetus might have antigens that are
not present in the mother's cells, allowing her to make antibodies against any fetal red cells that cross the placental barrier into the mother's circulation.

brachydactyly [Greek brachys
short + daktylos finger.] A rare dominantly inherited
condition in which the fingers and toes are short. This was the first trait
in humans shown to be transmitted according to Mendelian rules (W. C. Farabee,
1903). There are several different forms of brachydactyly. Additional information
is available in OMIM.

BRCA1 [Breast cancer locus 1; chromosome 17.] The first gene identified that is associated with increased risk of breast cancer. Women heterozygous for defective BRCA1 are likely to acquire the additional somatic mutations that cause progression to breast cancer. They also are at risk for ovarian cancer. Families in which defective BRCA1 is segregating typically show multiple cases of breast cancer, consistent with dominant inheritance with incomplete penetrance. For additional details, see OMIM.

BRCA2 [Breast cancer locus 2, chromosome 13.] The second locus identified that is associated with increased risk of breast cancer. In families in which variant BRCA2 is segregating, heterozygous males have increased risk of breast cancer (unlike BRCA1), but there is no increased risk of ovarian cancer (also unlike BRCA1). For additional details, see OMIM.

Brunner syndrome An X-linked recessive trait characterized by mental retardation, impulsive and aggresive behavior, and poor judgment. The defect is in the monoamine oxidase A gene. Only one family, in Holland, has been identified with this mutation. Additional information is in OMIM.

C-terminus The last amino
acid to be added to a polypeptide chain.
Starting at the N-terminus, amino acids are added
one-by-one, joined with peptide bonds. The
amino acids being added during chain growth always have a free carboxyl
group until another amino acid is added. The C-terminal amino acid keeps
its free carboxyl group, otherwise it wouldn't be the last one added, would
it?

cancer A malignant tumor. Such tumors can spread to other parts of the body and can invade other tissues.

carbon [Symbol C; atomic
number = 6; atomic mass = 12.011.]
One of the common elements, especially important
in biological systems. Carbon can form stable covalent bonds with
a number of elements, generating a vast number of different kinds of molecules.
Molecules that include carbon are described as organic molecules,
reflecting an earlier and false notion that they could be made only in
biological systems.

carboxyl group A functional
group that consists of a carbon atom to which one oxygen is bound with
a double bond and a hydroxyl group is bound
with a single bond. The remaining single bond of the carbon is attached
to other atoms. The structure is often written –COOH, with the understanding
that the first O is connected to the C with a double bond and the second
is connected to the C with a single bond. An important characteristic
of a carboxyl group is the propensity for the H to give up the electron
that it shares with the O and become a hydrogen ion,
H+. The remaining part of the molecule would then have
a negative charge. High concentrations of hydrogen ions constitute
acidity, and the carboxyl group is thus an acidic group. Any molecule
with a carboxyl group is potentially an acid. When you sip vinegar (You
do, don't you?), the acid taste is due to hydrogen ions released by the
carboxyl groups of acetic acid.

carcinogen A substance that causes cancer. Use of the term is usually restricted to environmental agents, such as radiation and chemicals, although some of the products of normal metabolism may also be carcinogenic. In most cases, carcinogens are also mutagens, and it is the increase in mutation rates that account for the increase in cancer following exposure.

catalysis [Greek katalysis
dissolution.] An increase in the rate of a process in the presence of a
substance (the catalyst) that itself is not consumed in the process. There
are many types of catalysts. In biological systems, enzymes
function as catalysts.

cation [Pronounced CAT-eye-on,
more or less.] A negatively charged atom or molecule.
See ion.

cDNA DNA that has been generated by reverse transcriptase acting on RNA templates, especially messenger RNA. This procedure allows mRNA to be isolated from cells or tissues and copied into DNA, thereby revealing which genes are actively transcribed in those cells or tissues. Since the template is mRNA, only the exons are represented in the cDNA. [Note: the c of cDNA stands for complementary, meaning complementary to RNA. Not the best choice for a name!]

cell The basic unit of life. Cells
can divide to produce more cells. Other structures, such as viruses and
mitochondria, can do so only within a cell. Cells are surrounded by plasma
membranes, which enclose cytoplasm, nuclei,
and other organelles

cell cycle A term that refers to the
sequence of stages in the life of a cell, including its replication. Following
cell division, a cell is said to be in the G1 phase. For most
mammalian cells, this is the predominant period in the life of a cell.
A cell in G1 that is not scheduled to divide again may go into
a more permanent phase called G0. Cells in G1 that
are ready to enter into division must first make a copy of the DNA.
This period of DNA synthesis is called the S phase. When synthesis is completed,
the cell is in the G2 phase for a short period. Division of
the nuclear contents occurs in mitosis or meiosis,
known as the M phase. At the completion of M phase, cytokinesis
usually results in division of the cytoplasm,
and two daughter cells are formed. Tthe daughter cells are again in G1.

cell hybrid When two cells fuse,
they form a cell hybrid. This happens rarely in nature but can be induced
in the laboratory between cultured cells, even between cells from very
different organisms. Thus it has been possible to make mouse/elephant hybrids
and animal/plant hybrids. The two nuclei from the parental cells fuse to
form a nucleus that has the full chromosome complements of both. For example,
a mouse/human hybrid has nuclei with 46 human chromosomes and 40 mouse
chromosomes. Cell hybrids have been very useful in assigning human genes
to specific chromosomes because of the tendency in such mouse/human hybrids
to lose the human chromosomes at random. If retention of a specific human
gene can be associated with retention of a specific human chromosome, the
locus for the gene must be on that chromosome.

cellular immunity Specific Immunity that is based on direct interaction of receptors on the surface of T-lymphocytes with an antigen. The T-cell receptors are similar to antibodies in that they are highly diverse and can combine only with specific target antigens. As in the case of antibodies, the diversity arises largely by programmed DNA rearrangement.

centimorgan A measure of the
distance between genetic markers, as measured by recombination frequency.
One centimorgan (cM) = 1% recombination = 1 map unit. Named after Thomas
Hunt Morgan, one of the American pioneers of genetics. See genetic
map.

-centric A combining form meaning center.
As used in genetics, it often refers to centromeres. Examples: metacentric,
having a centromere in the middle of the chromosome; acentric, lacking
a centromere.

centromere [Latin centrum center
+ Greek meros part.] The position on a chromosome
at which the spindle fibers attach in cell
division. The centromere is the last part of the chromosome to divide.

chemical bond An attractive
force between two atoms that holds them together.
There are several different kinds of bonds, depending on the nature of
the force. Examples are ionic bonds, covalent
bonds, and hydrogen bonds.

chimera [Greek khimaira
female goat.]An individual that results from fusion of
two genetically different embryos or that has incorporated tissues from
a genetically different individual. This happens rarely in humans
but has been recorded in several persons. Several mechanisms appear
to be involved, such as fusion of two zygotes, fertilization
of a polar body, etc. In the case of dizygotic
twins, chimerism of the blood cells can result from joining of the
blood circulation during embryonic or fetal development, with transfer
of blood-forming cells from one twin to the other. The recipient
thus has two genetically different populations of blood-forming cells and
may have a mixture of two blood types.
Contrast with mosaicism, in which the individual
arises from a single zygote, and the differences are due to somatic
mutation. See also knockout mouse.

chimpanzee One of the great apes, a member of the genusPan. There are two species, the common chimpanzee (Pan troglodytes) and the rare pygmy chimpanzee (Pan paniscus), both of which are native to Africa. Chimpanzees are thought to be the closest relatives of of humans, with a common ancestral line that split into the hominid and chimpanzee lines some 5 to 8 million years ago.

chorionic villi The
outer layer of the embryonic and fetal membranes is the chorion.
In the early embryo, the chorion has many extensions
(villi, sing. villus), some of which invaginate into the uterine
endometrium to form the placenta. Those that are not involved in
this process eventually disappear. Since the villi are derived from
the same zygote as the embryo, they should be genetically identical to
the embryo. Those that are not involved in formation of the placenta
can therefore be used as a genetic surrogate for the embryo in prenatal
diagnosis. They are usually collected at 8 to 10 weeks gestation,
and the cells can be analyzed directly by PCR
or cultured.

chromatid One of the two replicated copies
of a chromosome prior to division of the centromere.
The two chromatids that originate from the same chromosomes are sister
chromatids. Those that originate from two homologous chromosomes are nonsister
chromatids. In mitosis, sister chromatids should be identical. Nonsister
chromatids will differ in specific allele combinations, as do any pair
of homologous chromosomes.

chromatin [Greek chroma color.]
The materials in nuclei that are readily stained by certain dyes. Chromatin
is now known to be equivalent to chromosomes
in a dispersed state. Chromosomal regions that stain very readily are designated
as heterochromatin, and those that
stain less are called euchromatin. Most
genes appear to be within the euchromatic regions.

chromosome [Greek chroma + soma
body.] The nuclear structures in which genes are located. They consist
primarily of DNA, in which the genes
are encoded, and protein. A chromosomes is divided
into two arms by the centromere.

chromosome painting
The staining of chromosomes with fluorescent probes
that are specific for individual chromosomes. By using a variety
of fluorescent dyes on the probes, one can generate chromosome spreads
in which each chromosome fluoresces a different, unique color. This
technique is especially useful in detecting chromosome
rearrangements.

chromosome rearrangement
The physical breakage of one or more chromosomes followed by rejoining
in incorrect configurations. Common rearrangements are deletions,
duplications, inversions,
and translocations. Other, more complex
rearrangements are also observed.

chromosome theory
of inheritance The proposal (1902) that chromosomes are the physical
entities responsible for transmission of genes. Although the term theory
suggests that other possibilities may still exist, nearly a century of
research has left no plausible alternative.

clone Any group of cells or individuals that have descended from a single cell by asexual reproduction. Since no genetic recombination occurs with asexual reproduction, all members of a clone are genetically identical. See also DNA clone.

cloning vector A plasmid, often extensively modified, that has the ability to replicate inside bacterial cells and into which DNA of interest can be inserted. Selecting such a bacterial cell and culturing it to very large populations of cells constitutes DNA cloning.

codon A sequence of three nucleotides that code for one amino acid in a polypeptide. Of the 64 possible codons, 61 code for amino acids and three for chain termination.

codominant Two alleles are described
as codominant if both are expressed in a heterozygote.
Example: blood group AB is produced when a person is heterozygous for the
alleles for A and B.

collagen A group of related
structural proteins that are secreted by cells to form the extracellular
matrix that holds cells together. There are a number of types of
collagen and collagen genes. Mutations cause a variety of phenotypes,
depending on the particular gene and on how important that gene product
is in collagen formation in a particular tissue.

complementary Descriptive
of things that differ but together form a whole. A surface of a mold
and the items cast from it are complementary. A film negative and
the print made from it are complementary. The term is used to describe
the two strands of a DNA double helix.
The sequences of nucleotides on the two paired
strands are different, but pairing will occur only if an adenine
on one is opposite a thymine on the other, or if
a guanine on one is opposite a cytosine
on the other. Thus the information on one strand, i.e. the sequence
of nucleotides, determines the sequence of nucleotides on the other strand.
No additional information is present in the second strand.

complete hydatidiform mole
An abnormal pregnancy in which the implanted "embryo" consists only of
placental-type structures. The embryo is completely missing. Genetic
analysis indicates that the nuclear genes are entirely paternal and homozygous.
This would happen if an X-bearing sperm fertilized an enucleated egg (i.e.
an egg lacking a nucleus), and the haploid male
pronucleus doubled to produce a diploid
cell. The mitochondria are maternal, as expected.
These observations are consistent with the need for both a maternal and
paternal genetic contribution, presumably because of genetic
imprinting.

complex inheritance
Inherited variation in phenotype
that is attributed to combinations of alleles
at multiple loci.

compound heterozygote
An individual who is heterozygous for two different,
nonwildtype alleles. In particular, many
persons who are "homozygous" for a recessive trait are found on examination
of the DNA to be heterozygous for two different alleles, neither of which
is functional.

congenital adrenal hyperplasia
An inherited defect (autosomal recessive) in production of adrenal hormones.
The block in biosynthesis of the adrenal hormones shifts the steroid
precursors into the sex hormone pathway, increasing especially the synthesis
of androgens. This causes masculinization of affected
children.

congenital defect
Any defect that is present at birth, regardless of its cause.

consanguineous Descriptive
of a mating between related persons. The offspring of such matings have increased likelihood of being homozygous for alleles because of common descent. [This frequently mispronounced word
has five syllables, with the accent on the third: con.san.GUIN.e.ous.]

constant region The C-terminal part of the H and L polypeptides in antibody molecules. In contrast to the N-terminal regions, the antibodies from an individual have only half a dozen or so different amino acid sequences in the C-terminal region.

continuous trait A trait whose
variations are measured with a scale rather than by classification into
categories. Examples: height, weight. Persons may be described as tall
or short, but these generally refer to regions on the distribution curve
of height rather than to distinct categories.

coupled Two alleles of interest are said
to be coupled if they are on the same chromosome. See
repulsion.

covalent bond A chemical
bond in which electrons of two atoms are shared, producing a stable
link between the atoms. Each element has its
characteristic number of possible covalent bonds, called valence.
Among the elements of special biological interest, hydrogen can form one
bond, oxygen two, nitrogen three, carbon four, and phosphorus five.
Two atoms may be connected by a single covalent bond, by a double bond,
or by a triple bond, so long as the valence is not exceeded. Atoms
with fewer bonds can exist but are very unstable.

cri-du-chat syndrome
[French cri-du-chat cry of the cat.] A syndrome that results
from deletion of the distal part of the short arm
of chromosome 5. The other chromosome 5 is normal. The karyotype
formula is 46,XX, 5p– (for an affected female). Persons with
this deletion are severely mentally retarded. Most have an unusual
cry as young infants, one that sounds to human ears like a cat meowing.
Additional information and links are available on OMIM.

cross A term, used especially in experimental
genetics, referring to specific types of matings.

crossing over Exchange of chromosomal
segments between nonsister chromatids of homologous
chromosomes that occurs during prophase I of meiosis.
This generates new chromosomal combinations of alleles.

cystic fibrosis An autosomal recessive
disorder in humans that results from impaired ability to regulate chloride
transport across plasma membranes. This interferes with secretion of various
glands, with loss of salt in the sweat and inability to clear the lungs
of mucous. The last, in particular, leads to respiratory infections. Children
with cystic fibrosis usually do not survive beyond the second decade, and
few survive the fourth decade. In spite of this, the disease is rather
common among populations of European descent, with a frequency of ca. 1/2500
live births. Thus, ca. one person in 25 is heterozygous for a CF allele.
It has been suggested that heterozygotes have a survival advantage that
offsets the lethality of CF homozygotes. There is evidence that the advantage
may be survival of typhoid fever. Additional information on CF is available
in OMIM,
as are links to other resources.

Darwin Charles Darwin (1809-1882), along with Alfred Russel Wallace, proposed in 1858 that natural selection is the driving force of evolution. His 1859 publication, On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life, is regarded by many as the most influential book of the Nineteenth Century, though actually read by few. Its premises permeate all biological thought today and have been used by diverse social and political groups to support their views, even those that are diametrically opposed, such as Marxism and unbridled capitalism.

degenerate code Any
code in which more than one symbol or combination equates to the same item.
The genetic code is degenerate because the
same amino acid may be coded by more than one
codon. This is not surprising, because only
20 amino acids are coded by 61 codons.

deletion Loss of a segment
of a chromosome. Common mechanisms are
(1) two breaks in a chromosome, with loss of the middle segment prior to
joining and repair of the two end segments; (2)
unequal crossing over, which produces a deficiency (deletion) in one
crossover product and a duplication in the other.
The size of the deletion can be a single nucleotide
or a large number of nucleotides that includes many genes.

denature To disrupt the normal (native) structure of a protein or DNA. In the case of proteins, the tertiary and secondary structures are destroyed, typically by heat or acid, leaving only the primary structure held together by covalent bonds. In the case of DNA, the hydrogen bonds that hold the double helix together are broken, leaving single strands of DNA. The conditions used to denature proteins and DNA are not sufficient to break covalent bonds but can break other types of bonds. Cooking an egg is an example of converting native proteins, which are soluble, into denatured proteins, which are insoluble.

dental arch The form of the tooth row. During hominid evolution, the dental arch has changed from U-shaped to a more paraboloid shape.

deoxyribonucleic acid (DNA)
The molecule that serves as the primary repository of genetic information.
DNA occurs almost exclusively in the nuclei of eukaryotes, with very small
amounts in mitochondria and, in plant cells, in chloroplasts. DNA is a
polymer of deoxyribonucleotides. The bases that occur in DNA are adenine,
guanine, cytosine, and thymine. In cells, DNA most often occurs as a double-strand
structure, as proposed in the Watson-Crick
model.

deoxyribose A five-carbon
sugar that occurs in the nucleotides
of DNA. As the name suggests,
deoxyribose has one fewer oxygen atoms in its structure
than does ribose.

development "Development is a continuous
process that begins when an ovum is fertilized by a sperm and ends
at death. It is a process of change and growth which transforms the
zygote, a single cell, into a multicellular adult human being." [K.
L. Moore, The Developing Human, Saunders, 1973, p 1.] Included in
this definition is differentiation, the
generation of different kinds of tissues from a zygote,
and organization of the different tissues into functioning organs.

diabetes mellitus [Latin diabetes siphon + mellitus honey.] A condition in which lack of regulation of blood sugar (glucose) leads to a variety of metabolic problems. The term diabetes refers to the high volume of urine produced, and mellitus refers to the sweetness caused by glucose. The basic problem is lack of production of insulin by the pancreas or lack of effectiveness of insulin produced. Diabetes mellitus can be classified into type I and type II. Type I is typically early onset, in the early teens, but may occur at any age. The cells in the pancreas that produce insulin are destroyed by antibodies in an autoimmune reaction, thought to be induced by infection of those cells by a virus. Affected persons are dependent on external sources of insulin for survival, and this form is sometimes called insulin-dependent diabetes. Type II typically appears in late middle age but can appear much earlier. Insulin is still produced but not in necessary quantities nor does it regulate glucose effectively. The disease can often be managed purely by diet, but frequently insulin supplements are required. Type II is also known as insulin-independent diabetes, though that is a misnomer for some patients. The risk of acquiring either type I or type II is in part hereditary. In the case of type I, certain haplotypes of the MHC complex predispose to developing the disorder. In the case of type II, specific genes have not been identified, and the risk is probably multifactorial. There is strong clustering in families, however, including successive generations, which suggests dominant effects. There is also marked differences in frequency of type II in different populations, Native Americans being especially at risk. The high frequency of type II in many populations has led to the suggestion that type II may be the result of "thrifty" gene(s), that is, it may have had selective advantage under primitive hunter-gatherer societies in which life tended to be feast or famine. Additional details are available in OMIM.

Diego blood groups A polymorphicantigenic system on the surface of red blood cells due to a locus on chromosome 17. Two codominantly inherited antigens are recognized: Di(a) and Di(b). Di(a) was first found in Venezuela in a person with American Indian ancestry. Subsequently, it was found that Di(a) occurs primarily in Asians and American Indians and is found rarely in other populations, who typically have only Di(b). Additional information can be found in OMIM.

differentiation The generation
of different tissues from one or a few cells. Differentiation involves
turning some genes on and others off in a programmed manner, often strongly
influenced by signals from other cells. A zygote is described as "totipotent,"
meaning that it has the potential to differentiate into any cell type.
This is also true of many cells of a very early embryo. As differentiation
proceeds, however, cells of mammals typically lose totipotency. At least,
we do not know how to reverse differentiation. The great significance of
cloning, a la Dolly, is that differentiation was reversed. However, we
still do not understand differentiation at the molecular level, and it
remains to be seen whether cloning can be carried out using nuclei from
a variety of tissues and whether the conditions for reversing differentiation
can be defined at the molecular level and extended.

dihybrid cross A cross,
particularly in experimental genetics, between two parental stocks that
differ at two genetic loci of interest. Dihybrid crosses
are useful in determining whether the two loci segregateindependently.

diploid Having two sets of chromosomes.
In humans, diploid cells have 46 chromosomes (two sets of 22 autosomes
plus a pair of sex chromosomes, either two
X chromosomes (females) or one X and one Y (males). All somatic
cells are diploid. Germ cells are diploid prior
to the first division of meiosis but are haploid
following the first meiotic division.

direct gene count Counting the alleles in various genotypic combinations in order to establish the overall allele frequencies. In order to do a direct gene count, each genotype must be recognizable. This occurs only if all alleles are codominant.

discontinuous trait A trait
whose variations fall into distinct categories rather than positions on
a continuous scale. Examples: male/female, presence or absence of an extra
digit.

disjunction The separation of homologous
chromosomes during mitosis or meiosis. (In meiosis
II, the separation involves sister chromosomes.) Disjunction assures
that each daughter cell receives an equivalent complement of chromosomes.
An error in chromosome separation (yes, it happens!) is called nondisjunction.

distal Refers to some event
that is farther away from the centromere than some specified marker
or landmark.

dizygotic The term applied to twins who
are derived from two separate zygotes.
They are genetically dissimilar and are also called fraternal twins or
DZ twins. They arise when two or more ova are released at the same time
and are fertilized. They have the same genetic relationship to each other
as any pair of siblings. DZ twins cluster in families to some extent. Therefore
the tendency for DZ twinning appears to be inherited in part. The use of
"fertility" drugs increases the release of multiple ova and therefore of
dizygotic twins and other multiple births.

DNA clone A bacterial cell, usually E. coli, into which foreign DNA has been inserted, typically by means of a plasmid (cloning vector). Very large quantities of the inserted DNA can be prepared in this way.

DNA fingerprint A term used originally to describe a genetic profile based on certain minisatellite genetic markers. If a sufficient number of markers is used, a particular combination of markers would be as characteristic of an individual as a fingerprint (except that monozygotic twins would have identical genetic profiles, though not quite identical fingerprints).

DNA hybrid A double-strand DNA segment in which the two strands are from different sources. The strands must, of course, be complementary.

DNA library A culture of genetically engineered bacteria into which have been incorporated vectors that contain restriction fragments from a specified source of DNA. The cells would need to be cloned, i.e. spread on solid medium at high dilution so that colonies arise from individual cells. Colonies are then tested individually to locate those with particular DNA sequences inserted. The term library is appropriate in the sense that the culture has a huge variety, sometimes hundreds of thousands of bacteria, each distinguished by its foreign DNA. But it is like a library in which the books are shelved at random. Finding the right book, or bacterial colony, depends on identifying the colonies that bind a specific DNA probe.

DNA polymerase An enzyme that
catalyzes the assembly of DNA polynucleotides from the four deoxyribonucleotides.
In DNA replication, the full name of the enzyme is DNA-dependent DNA polymerase,
reflecting the fact that the template is DNA. RNA can also serve as a template
if RNA-dependent DNA polymerase (commonly called reverse
transcriptase) is present. DNA polymerase catalyzes the addition of nucleotides only to the 3' end of a polynucleotide strand that is complementary to and already bound to the DNA template.

DNA primer A short segment of DNA that is complementary to one end of a DNA strand to be copied and that provides a 3' end to initiate assembly of the new strand by DNA polymerase. The primer would thus form the 5' end of the new strand.

DNA probe A short segment of single-strand DNA that is labeled and that can be used to detect the presence of DNA that contains a sequence that is complementary to the probe. The label often is 32P (a radioactive isotope of phosphorus) but fluorescent labels also are now available. The size of the probe may be as few as 10-20 nucleotides or may be several hundred. DNA probes are used to test genetically engineered bacterial colonies to see which have incorporated a specific DNA fragment, to show the presence of a specific fragment in a mixture of fragments (Southern blot), or to show the presence and location of a specific gene on a chromosome (FISH).

DNA sequence The order
in which nucleotide pairs occur in a segment
of DNA. There are several methods for establishing a DNA sequence. The most prevalent methods are based on making copies of a DNA strand using DNA polymerase as the catalyst. In the presence of small amounts of a nucleotide analog, usually one that lacks a 3' hydroxyl, the analog will be incorporated but extension of the strand stops. This indicates which nucleotide is present at that position.

dominant An allele that is
expressed phenotypically when in combination with a different allele.

double helix A helix formed
by two strands intertwined to form a spiral. The common form of DNA
is a double helix. See Watson-Crick.

Down syndrome A syndrome
due to trisomy for chromosome 21; also called trisomy-21
syndrome. Affected persons are mentally retarded and have various
other features, including somewhat short stature, epicanthal folds, characteristic
fingerprints and flexion creases in the palms, and large tongue.
Most die in utero, but those who are liveborn have good life expectancy.
They have high risk of leukemia, one of the frequent causes of death, and
they are subject to respiratory infections, another frequent cause of death.
Some 5% of cases are due to unbalanced chromosome
translocations rather than simple trisomy. The imbalance generates
three copies of the long arm of chromosome 21, leading to the same gene
dosage imbalance as trisomy 21.

ductus deferens The duct that leads
from the epididymis and through which spermatozoa
pass, joining with secretions of the seminal vesicles to form semen.

Duffy blood groups A polymorphicantigenic system on the surface of red blood cells, coded by a locus on chromosome 1. Most populations have two common alleles, FY*A and FY*B, that are expressed codominantly. African groups have a very high frequency, often approaching 100%, of a third allele, FY, that is associated with lack of antigen. The Duffy blood groups are the receptors on red cells that allow infection by the malarial parasite Plasmodium vivax. Africans who are homozygous for the FY allele are resistant to this form of malaria. Additional information is available in OMIM.

duplication A repeated
chromosomal segment. The most common way of producing a duplication
is by unequal crossing over. This
produces a chromosomal status sometimes called partial trisomy
if the duplicated segment is large. The phenotypic
effects of duplications depend on the specific imbalance of genes created
by the duplication.

electron A subatomic particle
that has a negative electrical charge. The unit negative charge on
one electron is equal to the unit positive charge of one proton.
Electrons occur in shells surrounding the atomic
nucleus. They form the various types of chemical bonds
that join atoms.

electrophoresis The separation of charged molecules (ions) in an electric field. Under the alkaline conditions ordinarily used, DNA and most proteins have a negative electrical charge (anions). They move toward the positively-charged electrical pole and away from the negative pole. Molecules with different charge densities separate from each other because of their different rates of movement. Gel electrophoresis is a variation that is especially useful in separating DNA or protein molecules. The gel forms a matrix that acts somewhat like a sieve, separating molecules on the basis of size. In the case of DNA, the charge density is uniform, and size alone separates different polynucleotides, even those that differ by a single nucleotide. The mobility of proteins in gel electrophoresis is dependent both on charge and size.

element A basic unit of matter,
consisting of atoms with the same atomic
number. Over 100 elements are known, some of the largest being manmade
and very unstable. Only a portion are important in biological systems,
and most biological molecules are built only from
some half dozen different elements. Among the most common elements
in biological systems are carbon, hydrogen,
oxygen, nitrogen, phosphorus,
and sulfur.

elliptocytosis A rare
autosomal dominant trait in which red blood cells have an elliptical shape
rather than the usual biconcave disk shape. The defect is due to mutations in any of several genes that code for proteins that normally interact to form a skeletal structure on the interior of the red cell membrane.
Descriptions of the various genes involved can be found in OMIM.

embryo The initial stage of development.
In mammals, the term is applied to the inner
cell mass through the point at which all major structures are present
(the end of the seventh week in humans). After that point, the developing
organism is called a fetus.

endocytosis The transport
of materials into a cell by their binding to receptors, which then form
a concave "bubble" into the cell. Since the transported materials
do not have to pass through a plasma membrane,
they can be of quite large size. The process is facilitated by the
presence of specific receptors in the plasma membrane
that bind the substances to be transported.

endoplasmic reticulum
Membranous structures that occur in the cytoplasm of eukaryotes. Many are
heavily loaded with ribosomes (rough endoplasmic
reticulum) and are the sites of protein synthesis.

endoreduplication
Replication of chromosomes without subsequent
division of the cell. The result, in the case of a diploid
cell, is a tetraploid cell.

enzyme A biological catalyst.
The great majority of catalysts are proteins and
are thus the product of genes. Some RNA molecules are also known to have
catalytic activity (ribozymes). Each enzyme is highly specific in
the kind of reaction that is catalyzed and may be very specific in the
substrate on which it acts. The ending -ase
is indicative of an enzyme. For example, a polymerase is an enzyme
that catalyzes the formation of polymers from the subunits. See DNA
polymerase. Some of the earliest enzymes identified were given names
prior to the "-ase" rule, and the old names are still used, e.g. trypsin,
pepsin.

epididymis The tubular structure
into which spermatozoa pass from the seminiferous
tubules for maturation and storage. They pass from the epididymis into
the ductus deferens (vas deferens).

epigenesis The idea that embryonic development
occurs by the production of complex structures from simple structures.
Epigenesis is the opposite of preformation.
The current view that the fertilized egg carries instructions for the development
of complex organs and tissues is an example of epigenesis.

Escherichia coli
The common bacterium of the colon. E.
coli is also the most widely used bacterium in laboratory studies of
prokaryotes because of ease of cultivation and
the fact that it is not associated with disease. (Recent news reports
have given a bad name to E. coli because of pathogenicity of some
exceedingly rare strains. But everyone reading those reports already
has a gut full of the common, benign strains.) Because E. coli
has been used in so many experiments, more is known about it than any other
bacterium. Therefore, it was selected as one of the target organisms
for complete DNA sequencing. The sequence
was completed in 1998, making it one of the few organisms for which that
is true.

estrogen [Latin oestrus, Greek
oistros gadfly, passion, frenzy] Any of several related steroids
that promote development of female genitalia and other sexual characteristics
and that are increased in the menstrual cycle preceding ovulation. Estrogens
are produced primarily in the ovaries but are also produced in both men
and women by the adrenal glands.

eugenics The improvement of the population
by "good genetic practices." The eugenics movement started in the late
19th Century, primarily in the U.K., and spread to Germany and the U.S.
The basic premise was to encourage persons with desirable genetic traits
to have lots of children and to encourage those with undesirable genetic
traits not to reproduce. Far too little was known about the inheritance
of human traits to allow any such program to be successful, quite apart
from the moral and ethical issues raised.

expressivity The phenotypic variation
that is associated with a specific genotype.

F1 The first filial generation.
The designation for the offspring of a cross between two parental stocks.

F2 The second filial generation,
ordinarily produced by intercrossing the F1 generation among
themselves.

fallopian tube The pathway that
leads from the ovary to the uterus. Ova
released by rupture of an ovarian follicle
enter the fallopian tube, where they may become fertilized if spermatozoa
are present. The developing embryo then migrates over a period of several
days into the uterus, where implantation in the endometrium occurs.

familial hypercholesterolemia
(FHC) A dominantly inherited condition that causes high levels
of plasma LDL (low-density lipoprotein).
The problem is caused by defective LDL receptors.
This interferes with cell uptake of LDL, which in turn leads to greater
synthesis of cholesterol. Persons who
are heterozygous for an allele that causes defective LDL receptors have
greatly elevated blood cholesterol, with high risk of coronary disease.
Most have major heart attacks in middle age, some as young as the thirties.
The frequency of heterozygotes in the general population is ca. 1/500 persons.
Therefore, this condition is not the major cause of high cholesterol and
heart disease. Homozygotes are rare, ca. 1/250,000, and have much
higher levels of blood cholesterol than do heterozygotes, even as very
young children. They are at high risk of heart disease during childhood,
and few survive. Homozygosity for FHC is one cause of the need for
heart/liver transplants, the heart because of the damage that has occurred
and the liver because that is the primary organ in which cholesterol synthesis
occurs. Liver transplants in this case are a form of gene
therapy, even though it be low tech by genetic engineering standards.

fetal alcohol syndrome A condition in newborns due to large consumption of alcohol by the mother during pregnancy. Such children have a typical facial appearance, including a flat nose and wide-set eyes, and they are mentally retarded.

fetus The developing
organism, from the embryonic period to birth. In
humans, the fetal period begins at the eighth week of gestation.

fibrillin [Gene symbol FBN1] A protein that is an important component of the extracellular matrix in connective tissue. Defects in fibrillin are responsible for Marfan syndrome. The FBN1 locus is on chromosome 15.

fibroblast A rather generalized cell
type found widely distributed in various tissues of mammals. Fibroblasts
grow well in the laboratory, which, with their wide distribution, makes
them very useful in chromosome studies.

5'-flanking region
The region of DNA adjacent to the 5' end of the coding region of a gene.
This region, outside the coding region, regulates the rate of transcription.

fluorescence in
situ hybridization (FISH) A technique for revealing specific
DNA sequences, applied to chromosome spreads and tissue sections.
The technique uses a probe that consists of a DNA
segment to which is attached fluorescent dyes. The DNA in the chromosomes
or tissue sections is denatured, usually by heat, to separate the two DNA
strands. The probe is added, and conditions are adjusted, usually
by lowering the temperature, to allow reannealing of complementary
DNA. Because of excess of probe, any DNA that is complementary to
the probe will reform double strands with the probe rather than the original
DNA partner. Binding of the probe is detected by the fluorescence
of the attached dye. This method is very sensitive and can be used
with a chromosome spread to detect single genes.

folic acid One of the B vitamins, essential in the diet. Folic acid deficiency greatly increases the risk of neural tube defects in developing embryos.

foramen magnum The opening at the base of the skull through which the spinal cord enters the cranial cavity.

fossil A remnant or impression in rock of an ancient organism. Most fossils are the remaining hard parts, e.g. bones, of organisms that have been penetrated by minerals with subsequent hardening to rock-like structures, preserving the form of the original.

founder effect A shift in gene pool that occurs when a small number of individuals form a new population. The shift occurs purely by chance because the founding members of the new population do not happen to match exactly the allele frequencies of the parental population.

fragile site A marked
constriction in a chromosome that occurs under certain conditions of cell
culture. Also called a secondary constriction, the primary
constriction being the centromeric region.
Rather than being fragile, the sites are regions of diminished chromosome
coiling, giving the appearance of fragility. Some fragile sites are
very common; others are rare. Only two are associated with phenotypic
effects: fragile-X A (FRAXA) and fragile-X E (FRAXE), both near the end
of the long arm of the X chromosome. FRAXA is associated with marked
mental retardation in hemizygous males and marginal
retardation in heterozygous females.
FRAXA is due to trinucleotide expansion
in the untranslated 5' region of the FMR1 (familial mental retardation
1) gene on the X chromosome. Individuals with the "premutation"
form of the gene are phenotypically normal. If they are females,
they have a high risk of transmitting the "full mutation" form of the gene.

fragile-X syndrome
A condition that results from the full mutation of the fragile-X locus
(FRAXA) near the end of the long arm of the X chromosome. In males,
the syndrome includes marked mental retardation, a typical facial appearance,
and macrorchidism (very large testes). In heterozygous females, there
is mile mental retardation. The fragile-X syndrome commonly occurs
as a result of trinucleotide expansion
in the 5' untranslated region of the FMR1 locus. Rare cases have
been reported due to conventional mutations in the coding region of the
gene. Apparently the trinucleotide expansion leads to greatly reduced
translation of an otherwise normal FMR1 messenger
RNA.

frameshift mutation
A mutation that alters the translationreading frame. This happens when nucleotides
(except for multiples of three) are inserted or deleted within the coding
region of a gene. From that point on in the translation, the new
reading frame generates amino acid sequences
different from the original.

fusion gene
A gene that is a composite of two genes, generated usually by translocation.
One mechanism for inappropriate expression of a gene is chromosomal translocation
that places the coding region of the gene under
control of the promoter of another gene. In some
instances, the translocation breakpoint is within the coding regions of
the two genes, and the resulting protein may have an N-terminal
amino sequence that corresponds to the promoter but a C-terminal
sequence that is from another gene. If the bulk of the fusion protein is
from an oncogene and is functional in the cell, the consequences may be
similar to overexpression of the original oncogene.

galactose A sugar, similar to glucose, that is found in very low quantities in certain tissues of the body. It combines with glucose to form lactose, the sugar in milk. An inherited defect in metabolism of galactose causes galactosemia.

galactosemia An autosomal
recessive disorder caused by lack of the enzyme galactose 1-phosphate uridyl
transferase. As a result, galactose 1-phosphate accummulates and interferes
with other metabolic processes. Galactose occurs
in the diet in the form of lactose, which is the
sugar in milk. Infants placed on milk therefore are most subject to the
toxic effects. These include severe mental retardation, liver damage, cataracts,
and death. Removal of milk from the diet greatly reduces the problem. Galactosemia
is very rare and should not be confused with the common condition of lactose
intolerance. More information is available in OMIM.

gene A unit of heredity. Originally, gene
was used to describe a unit of phenotypic variation. It is also now used
to describe a unit of function, i.e., a segment of DNA from which a single
RNA molecule is transcribed. Ultimately, the two definitions merge as more
knowledge is gained of the molecular basis of hereditary variations.

gene amplification The condition in which a gene is copied many times, often in tandem, though not always. Even though a gene may be switched "off," there is often a very low rate of transcription. With hundreds or thousands of copies of the gene, the overall result may be substantial transcription. If the amplified gene is an oncogene, this can cause loss of regulation of cell growth. Gene amplification is found in many cancers, especially in the more advanced stages.

gene frequency The frequency of specific alleles in a population, without regard to how they are combined in individuals.

gene pool The alleles in a population, viewed collectively rather than combined in individuals.

genetic code The sequence
of DNA nucleotides that are translated
into amino acid sequences in proteins.
The code is a triplet code, i.e. a sequence of three nucleotides codes
for one amino acid. This unit of three nucleotides is called a codon.
Of the 64 possible sequences of three nucleotides, 61 code for amino acids.
The remaining three are stop codons, that is, when a stop codon is encountered
during translation, synthesis of that polypeptide chain is terminated.
The genetic code is universal, in the sense that the same code is used
by all forms of life, from viruses and prokaryotes to plants and animals.

genetic distance The distance
between two genetic markers as measured by recombination frequency. See
genetic
map.

genetic drift The shift in the gene pool of a population that is the result of purely random factors. The most important factor is small size of a population, which can lead to chance alterations of allele frequencies in succeeding generations. Genetic drift is to be contrasted with natural selection, in which variations in fitness among genotypes alter the gene pool.

genetic engineering A general term that refers to the assembly of DNA from different sources into single pieces of DNA, which then are cloned in bacteria or other vectors or inserted into the genome of an organism by some means.

genetic heterogeneity A general
term that reflects the fact that a particular phenotype may be due to different
loci or to different allelic combinations at a particular locus. For example,
the dominant trait elliptocytosis
is due to a locus on chromosome 1p in some families and to a locus on chromosome
1q in others.

genetic map A representation of the
location of genes or genetic
markers with respect to each other, based on recombination
frequencies. A genetic map is linear, and distances between loci are measured
in recombination percentage = map units = centimorgans. Contrast with physical
map.

genetic marker Any gene or other
DNA variation that is useful in tracking some genetic event. For most purposes,
the marker must be polymorphic.
In the case of a gene used as a genetic marker, it is the variation that
is of interest, not the gene function. Example: A blood group O man cannot
be the father of an AB child. In this example, the function of the
blood groups is irrelevant. It is the rules of their transmission that
provides an answer to the question posed. With the development of new DNA
technology, the majority of genetic markers are variations in DNA at sites
that may or may not be part of a gene. However, their transmission to offspring
follows Mendelian rules for codominant inheritance. They can be mapped
just as genes are mapped.

genetics The study of heredity.

genome A haploid complement of genes, used particularlyi in the abstract. Common usage also refers to the diploid complement of diploid organisms. ("He has a gene for stupidity in his genome.")

genomic library A DNA library generated from DNA fragments produced from the entire DNA (genome) of an organism. Nongenomic libraries would start with some fraction of the DNA, such as a particular chromosome or other large piece of DNA.

genotype The genetic constitution of an
organism, irrespective of the extent to which the genes are expressed in
the phenotype.

genotypic (genetic) ratio The ratio
of genotypes among the offspring of a genetic cross, irrespective of whether
the genotypes are distinguishable phenotypically.

germ cell Ova and sperm, or a cell that
has the potential to undergo meiosis and become
an ovum or sperm. Germ cells are set aside early in mammalian embryogenesis.
An event, such as mutation, must occur in a germ
cell in order to be potentially transmissible to offspring. All cells other
than germ cells are called somatic cells.

germinal mutation
A mutation that occurs in germ cells and that therefore can be transmitted
to offspring.

gibbon A small anthropoid ape, found in Asia. The gibbons are adapted for arboreal life, with long, thin limbs, the arms used for moving through the trees by brachiation. The gibbons are the most distant from humans of the anthropoids.

glucose A common sugar in all forms of life. Glucose is the major metabolic link between carbohydrates and fats. It is metabolized in cells, generating energy in the form of ATP. Glucose molecules are joined together to form starch in plants and glycogen in the livers of animals, both of which serve for energy storage. Glucose also polymerizes to form the structural (woody) component cellulose in plants.

glucose 6-phosphate dehydrogenase (G6PD) deficiency Inherited deficiencies of the X-linked gene that codes for G6PD. These deficiencies are common in Africans and in Mediterranean (Italian, Greek) populations, where the high frequencies are thought to be due to resistance of G6PD-deficient persons to falciparum malaria. Deficiency appears to be due primarily to reduced stability of the enzyme, which must function without replacement for the average 120 day life of a red blood cell. G6PD occurs in all cells, though replacement occurs to some extent in all but red cells. Deficiency in Mediterranean populations is due to an allele G6PD*MED, which produces severe deficiency, including tissues in addition to red cells. The condition known as favism results when such persons consume faba beans. There is mass destruction of red cells and damage to other tissues, often resulting in death. The African populations primarily have G6PD*A, which has a less severe potential for unpleasantness. The gene was first detected when African-American troops returning from the Pacific during World War II were given the synthetic antimalarial primaquine. Destruction of red cells occurred to some extent, followed by return to normal. Either allele creates a potential for sensitivity to a variety of drugs and other chemical agents. In African populations, there is also another polymorphic allele, G6PD*A+, which is a normal variant whose product is separated by electrophoresis from the product of the common G6PD*B allele. Since G6PD is on the X chromosome, only males, who are hemizygous for the X, are affected with the deficiencies. Heterozygous females sometimes show degrees of deficiency consistent with chance bias in inactivation of the normal X chromosome. The polymorphism of the G6PD locus has made it a useful genetic marker, first to support experimentally the hypothesis of X-chromosome inactivation in females, and second to prove that tumors are monoclonal. Further information on G6PD is available in OMIM.

gonial cell Cells in the germ line
that replicate by mitosis. In males, such cells
are spermatogonia; in females they are oögonia. Once
a gonial cell enters meiosis, it is designated a
spermatocyte or oöcyte.

gorilla One of the great apes, found in Africa. Both the genus and species names are gorilla; thus the binomial classification is Gorilla gorilla. The most common are the lowland gorillas, but there is also a smaller, rare mountain gorilla, considered to be a subspecies. Gorillas have marked sexual dimorphism, the size of mature males being ca. twice that of females. Next to chimpanzees, gorillas are the closest relatives of humans.

great ape Any of the large apes, i.e. orangutans, gorillas, and chimpanzees. The great apes are our closest relatives among the primates.

growth hormone A protein
hormone secreted by the pituitary gland that acts
on many other tissues to stimulate growth. The human growth hormone
gene is located on chromosome 17. Mutations that cause the growth
hormone to be nonfunctional cause one form of dwarfism when homozygous.
More details can be found in OMIM. Administration of GH from other
sources during childhood increases the growth of such persons.

haploid [Greek haploos single, simple.]
A term used to describe a single set of chromosomes.
A haploid set of human chromosomes consists of 22 different autosomes
and one sex chromosome, either an X or a
Y. Mature germ cells are haploid, but all other
cells in mammals are diploid.

haplotype A group of closely-linked genes
or genetic markers among which recombination is very low. Because of this, a specific combination of alleles within the group tends to remain together on the same chromosome through many generations.

Hardy-Weinberg equilibrium The case in which the frequencies of genotypes in a population matches those predicted by the Hardy-Weinberg law based on allele frequencies in that population.

Hardy-Weinberg law The application of the binomial expression to calculate probabilities of various genotype combinations based on allele frequencies in a random mating population. The binomial is written (p + q)2, where p and q are the frequencies of two alleles. If p + q = 1, which is the case if there are only 2 alleles, then (p + q)2 = 1. The expression can be expanded to p2 + 2pq + q2 = 1, where p2 is the frequency of persons homozygous for the allele represented by p, 2pq is the frequency of heterozygotes, and q2 is the frequency of homozygotes represented by q. For more than two alleles, the expression is (p + q + r + ... + z)2 = 1.

heavy chain One of the two types of polypeptide chains found in antibodies. See antibody for more details.

hemizygous [Greek hemi half +
zygous.] Having only one copy of a gene, chromosome, or chromosome segment.
Males are hemizygous for genes on the X chromosome, since they have only
one X chromosome. Similarly, if there is deletion of part of one chromosome
of a pair, the genes on the undeleted chromosome are described as hemizygous
if they are in the region that corresponds to the deletion of the homologous
chromosome.

hemoglobin The major protein
in red blood cells whose function is to bind oxygen in the lungs, transport
it to other tissues, and release it for use by the tissues. Hemoglobin
(Hb) is a tetramer, consisting of four protein
subunits, two identical alpha or alpha-like globins and two identical beta
or beta-like globins. Each subunit includes a complex non-protein
molecule called hemin, which gives Hb (and red cells) the red color
and which is the site of oxygen binding. Hemoglobins have been highly
instructive in understanding how genes function. The analysis of
sickle-cell Hb provided the first evidence
in any organism that different alleles code for different amino
acid sequences. Members of the families of alpha-like and beta-like
Hb genes are "turned on" at different stages of fetal and embryonic development,
providing the opportunity to study how such switching occurs. Many
of the hundreds of mutant forms of Hb are quite detrimental but nevertheless
occur at high frequencies in some populations. These illustrate the
complexities of natural selection in human
and other populations.

hemolytic disease of newborn (HDN) A condition in newborns due to production of antibodies by the mother against antigens on the child's red cells. This can only happen if the antigen is absent from the mother's cells. The most common occasion for HDN is when the fetus is Rh-positive and the mother is Rh-negative. Typically the mother does not become immunized against the fetal cells until the second such incompatible pregnancy. This is because the major introduction of fetal red cells into the maternal circulation occurs at the time of delivery. The immune response can be usually prevented
by injecting antibodies against the fetal red cells shortly after delivery, thus destroying them and removing them from circulation. The next incompatible pregnancy is thereby spared.

hemophilia A condition in which factors
necessary for clotting of blood are deficient or lacking. The most common
form is hemophilia A, which results from lack of coagulation factor VIII.
The gene for this factor is on the X chromosome at Xq28. Mutations are
recessive, with heterozygous females having normal blood clotting. Hemizygous
males bruise easily, have bleeding into joints, and bleed profusely from
small cuts. A less common form (hemophilia B, Christmas disease) is caused
by lack of coagulation factor IX, the gene for which is also on the X chromosome.
These two hemophilias are classic examples of X-linked recessive inheritance.
Links to these disorders can be found at OMIM.

heritability That part of the total
population variation in a complex
trait that is attributed to variation in genotypes.
The remaining part of the total variation is environmental. Since both
genotypic variation and environmental variation can differ among populations,
the heritability measured on a particular population applies only to that
population. Other populations may be more uniform or less uniform for the
genes that contribute to the trait, and the same may be true of environment.

hermaphrodite [Greek Ermafrodito,
son of Hermes and Aphrodite, who, according to mythology, merged with the
nymph Salmacis and thus acquired both male and female characteristics.].
An organism with both male and female genitalia. In modern medicine, a
person with both ovarian and testicular tissue. Persons with only ovaries
or testes but with some phenotypic traits of the other sex are pseudohermaphrodites.

heterodisomyUniparental
disomy in which the two chromosomes are derived from the two homologs
of the parent. They should be different in the centromeric regions
but can be identical in more distal segments due to crossing over in meiosis
I.

heterogametic Producing more than
one type of gamete with respect to sex chromosomes. In mammals, males are
heterogametic, producing both X-bearing and Y-bearing sperm. See homogametic.

heterozygous The presence of different
alleles at a specific locus on the two homologous chromosomes of a diploid
organism.

histone A basicprotein associated with DNA
in cells. There are several different histones, which join together
to form a structure around which DNA wraps ca. 1.75 times. Each such
DNA-histone structure is a nucleosome. In a single nucleus,
there is a vast number of nucleosomes.

holandric [Greek hol- whole +
andros man.] An older term for Y-linked, i.e. genes that are on
the Y chromosome and therefore are transmitted only by males.

hominid Any of the species, including humans, in the evolutionary lines after the separation from the common human/chimpanzee ancestor. These comprise the family Hominidae.

hominoid [Latin homo man + Greek oeidos likeness.] A member of the superfamily Hominoidea, which consists of the small apes, the great apes, and humans.

Homo [Latin homo man.] The genus that includes modern humans as well as early or archaic humans. The earliest fossils, from H. habilis, are from 2.4 million ybp (years before present) and extend to 1.6 million ybp. These all occur in east Africa. About 1.8 million ybp, a new fossil type, H. erectus, appeared and survived in Africa until some 400,000 ybp. H. erectus was the first hominid to move out of Africa, spreading widely in Asia where it survived to perhaps 200,000 ypb. About 400,000 ybp, the first members of our own species, H. sapiens, appeared in east Africa. These archaic forms spread out of Africa into Europe and the Middle East, giving rise to H. neanderthalensis, which survived until 30,000 ybp. Modern H. sapiens arose in Africa 100,000 to 200,000 ybp. Some moved out of Africa ca. 100,000 ybp, spreading to all other parts of the world.

homogametic Producing a single type
of gamete with respect to sex chromosomes. In mammals, females are homogametic,
with all gametes having a single X chromosome. See heterogametic.

homologous As commonly used in genetics,
homologous describes the two members of a pair of chromosomes
in a diploid organism. Members of a homologous pair
have the same array of genes, although the gene pair may vary slightly
in structure.

homozygous The presence
of identical (or similar) alleles at a specific genetic locus on the two
homologous chromosomes of a diploid organism.

homunculus The miniature
individual that the theory of preformation proposed to exist in germ cells.
The poor quality of early microscopes, coupled with the imagination of
the observers, led to reports that homunculi were visible. However, they
have not survived improved microscopes.

hormone A substance secreted
by an endocrine gland (e.g. pituitary, adrenal, gonads) into the blood stream and that regulates the activities
of tissues and glands in other parts of the body. Hormones typically
are proteins, small peptides (8 to 12 amino acids),
or steroids.

Huntington disease A deterioration of certain central nervous system functions that lead to choreiform movements (involuntary jerky movements) and loss of mental abilities. Huntington disease (HD) is inherited as a dominant trait with late onset,
usually in the fourth decade. The gene involved is located on chromosome 4p. HD is an example of trinucleotide expansion as the usual form of mutation. Additional information and links can be found in OMIM.

hybrid A cross or mating between
two genetically distinct parents. The parents may differ by only a few
genes, or they may belong to different but closely related species
(interspecific cross) when such crosses are possible.

hydrocarbon A chemical
compound composed entirely of hydrogen and carbon
atoms bound covalently. Examples are gasoline,
methane, and butane. They are very hydrophobic
and, generally being less dense than water, float on water without mixing.
There are many possible ways that H and C atoms can be combined without
violating the valence rules.

hydrogen [Symbol H;
atomic number = 1, atomic
mass = 1.008.] The smallest element.
There is one proton in the nucleus, and there are no neutrons in the common
form (isotope), although forms with one or two neutrons
exist.

hydrogen bond A weak
chemical attraction that occurs between the hydrogen of an amino
group or a hydroxyl group and the unpaired
electrons of another nitrogen or oxygen. The two molecules of which
these are a part must be in specific spatial orientations with each other.
Little energy is required to break hydrogen bonds: the temperature of boiling
water is sufficient. Indeed, the process of cooking an egg is primarily
one of breaking hydrogen bonds, allowing the polypeptide
chains to become randomly arranged rather than orderly. Hydrogen
bonds are crucial to DNA replication and
transcription and to formation of functional
proteins.

hydrophilic [Greek hydor water
+ philos loving] Descriptive of substances that mix readily with
water. Chemical structures that form ions or that are
rich in oxygen generally are hydrophilic. Examples: sugar, salt.

hydrophobic [Greek hydor water
+ phobos fear] Descriptive of substances that do not mix with water.
Examples: fats, petroleum.

hydroxyl group A functional
group consisting of the structure –O–H. It is usually connected
covalently to carbon. A hydroxyl group
is hydrophilic and increases the water solubility
of the molecule of which it is a part. If that carbon is connected
only to other carbons or to hydrogen, the hydroxyl group is often described
as an alcohol.

hypercholesterolemia The name means high levels of cholesterol in the blood. This description applies to many people, whose condition is due in part to diet and in part to heredity. Some 1 in 500 persons is heterozygous for familial hypercholesterolemia, in which blood values for total cholesterol are 250-450 mg/dl. In the rare
homozygotes, total cholesterol values are >500 mg/dl. Heterozygotes typically die of cardiovascular problems in middle age, whereas homozygotes die of heart defects as children. The problems are caused by defective function of the LDL (low density lipoprotein) receptor, which normally transports LDL-bound cholesterol from the blood into cells. The gene for the LDL receptor is on chromosome 19 at 19p13. Additional information and links are available in OMIM.

hyperekplexia Excessive startle response. The genetic defect is in the glycine receptor-1 locus on chromosome 5. Additional information is available in OMIM.

immune response The defense system of the body that combats foreign substances, such as bacterial and viral infections. There are two principal and related forms: humoral immunity and cellular immunity.
Humoral immunity consists of antibodies in the blood plasma that bind to specific foreign (nonself) antigens, causing them to be removed. Antibodies are produced by B-cells. Cellular immunity consists in attack and binding by T-cells. Both systems depend on specific recognition of foreign antigens, and both are dependent on DNA rearrangement to generate the variety of antibodies and T-cell receptors necessary to achieve the high level of specificity for diverse antigens.

imprinting As used in genetics, imprinting
refers to temporary inactivation of certain genes depending on the sex
of the parent from which they are received. For example, a particular allele
may become active in an offspring only if it is transmitted by the mother.
The normal paternal allele will not be active in the offspring. Therefore,
if the maternal allele is inactive because of mutation, neither will be
functional in the offspring. Imprinting is also a consideration in uniparental
disomy. If both chromosomes come from the same parent and happen to have
an imprinted region, then the genes in that region are inactive on both
chromosomes. The imprinting is reset each generation. Examples in humans
are Prader-Willi syndrome and Angelman
syndrome. There are few identified imprinted regions in humans, and
most chromosomes are known not to have them. Since some genes are imprinted
in the mother and other loci are imprinted in the father, an offspring
can develop normally only if if has a mother and a father. See parthenogenesis,
hydatidiform mole.

in vitro fertilization
(IVF) Although the name literally means "fertilization in glass" (in
a test tube), it is actually done in plastic containers. "In vitro" is
a time-honored phrase meaning to do things in the laboratory. In this instance,
the egg donor is induced by hormones to superovulate (release multiple
ova). The ova are collected surgically and are mixed with donor sperm.
Those that are observed microscopically to be developing normally are then
suitable for transfer into the female who is to serve as the gestational
mother (often but not always the biological mother). There are several
reasons for use of IVF, including diagnosis of genetic disorders in the
preimplantation embryo.

incomplete dominance This
term is applied to alleles that are expressed in heterozygous combination
with other alleles, but the heterozygous phenotype is different from that
of homozygotes for the allele.

independent assortment One
of Mendel's major findings that parental combinations of alleles at different
loci are not maintained during formation of gametes. With the discovery
that chromosomes are the basis for the physical transmission of genetic
traits, it became apparent that whether a chromosome is maternally or paternally
derived has no bearing on its distribution to daughter cells in meiosis.
In addition, crossing over generates new chromosomes
with combinations of maternally and paternally derived alleles. An exception
to independent assortment occurs if two genes are very near each other
on a chromosome, since the frequency of crossing over between them is low.

initiation codon The
codon that is used to initiate all translation.
This codon, AUG in RNA codes and ATG in DNA codes, codes for the amino
acid methionine. This means that at the time of translation, all
polypeptide chains begin with methionine at the N-terminus.
However, in most cases, the methionine is removed shortly thereafter and
rarely occurs in completed proteins. (See genetic
code.)

inner cell mass The mass of cells
in a very early embryo from which the embryo proper develops. The remaining
cells form the birth membranes.

inorganic molecule
Any molecule that does not include carbon
in its composition.

insertion Insertion of one
or more nucleotides into DNA at a specific point.
If this happens within the coding region of a gene, the reading
frame may be altered.

intelligence quotient Perhaps
better known as IQ, the intelligence quotient is derived by administering
a test of mental achievement that has been standardized for each age group
and then dividing the score by the chronological age of the subject (and
then multiplying by 100 to get rid of fractions.) A child who performs
at the exact average for his or her age would have an IQ of 100. Those
performing at a more advanced level than the chronological age would have
scores greater than 100. The fact that you are reading this means that
your IQ is probably greater than 100! There has been much argument about
the nature of intelligence and whether the tests used actually measure
intelligence. They do seem to measure something of which intelligence is
a component and to be somewhat predictive of academic ability.

interphase The part of the nuclear
cycle following the end of one division to the beginning of the next.
Interphase can be divided into three parts: G1, in which the
DNA has yet to replicate; S, the period in which DNA replication occurs;
and G2, the period between S and the beginning of mitosis
or meiosis.

interstitial cells In general,
cells located between other structures. Used especially to refer to the
cells in the testis that are in the space between
the seminiferous tubules. The interstitial
cells are the site of testosterone synthesis
in the testis.

intron A segment of DNA that
lies within the coding region of a gene but that does not code for amino
acid sequences. These segments, which are transcribed and therefore
are in the primary transcript, are removed
in the nucleus by a process called splicing.
When the introns are removed, the remaining segments (exons)
are joined together to form messenger RNA.

inversion A chromosomal rearrangement
in which there are two breaks in a chromosome, with inversion of the central
segment prior to chromosome repair. Usually there would be no loss
of genes, and therefore no effect on the phenotype. However, inversions
generate problems in meiosis, since specific chromosome pairing can occur
only by formation of an inversion loop. Crossing over within the
inversion loop can lead to unbalanced gametes.

inversion loop The loop
that results when homologous chromosomes, one with an inversion, pair.

ion An electrically charged atom
or molecule. The charge arises from loss
or gain of electrons in the outer electron shell
of an atom. In the case of loss of one or more electrons, which are
negatively charged, the remaining atom becomes positively charged because
of the positively charged protons in the nucleus.
In the case of gain of one or more electrons, the atom becomes negatively
charged. A positively charged atom or molecule is called a cation,
and a negatively charged atom or molecule is an anion.

ionic bond A chemical
bond that consists of the attraction between two ions
of opposite charge. Ions of the same charge, either positive or negative,
repel each other. Ionic bonds are not rigid and allow for frequent
exchange of partners or simultaneous attraction to two other ions.
A parallel would be a dance hall filled with equal numbers of heterosexual
males and females. There may be frequent exchange of partners, but
pairing would occur, at least for short periods.

isodisomy In the case of
uniparental disomy, both chromosomes
having the same centromeric and adjacent regions. In complete isodisomy,
the two homologous chromosomes would be entirely identical and therefore
homozygous for all loci. This would occur if the zygote were originally
monosomic, with duplication of the single chromosome to restore the euploid
state. If the two homologous chromosomes were due to nondisjunction
at meiosis II, only the regions near the centromere
would be identical because of crossing over in prophase I.

isogenic [Greek isos equal + -genic.] Having identical genotypes. The term is used especially in genetics to refer to strains of organisms, all members of which are genetically identical (except for sex chromosome differences). In mice, for example, many generations of brother-sister mating has produced a number of strains in which virtually all genetic variability has been eliminated within each strain. Such strains are useful in certain testing procedures where the confounding effect of genetic variability is to be avoided.

isotope A variation of an element
that has the same atomic number (i.e. the
same number of protons in the nucleus) but a different
number of neutrons. For example, hydrogen
may have [1p,0n], [1p,1n], or [1p,2n] nuclei. Since there is no difference
in the number of protons (and hence, electrons), all have identical chemical
properties and are the same element. However, the masses
differ because of the neutrons. The ratio of protons to neutrons
strongly influences the stability of the nucleus. In the case of
hydrogen, nuclei with either 0 or 1 neutron are very stable. However,
nuclei with 2 neutrons are unstable and disintegrate spontaneously, releasing
energy in the form of radiation. This isotope of hydrogen is therefore
a radioactive isotope. Most other
elements are similar, having one or more stable isotopes plus one or more
unstable isotopes. In the case of elements with high atomic numbers,
none of the isotopes may be stable.

karyotype A standardized array of chromosomes.
Typically, chromosomes are cut out from a photograph of a metaphase
spread and are then pasted into the appropriate position, starting with
the two chromosomes 1, followed by chromosomes 2, etc. Karyotypes are very
useful in evaluating the chromosome status of a person or of tissue samples
and cell cultures.

karyotype formula
A method for designating the karyotype of a person. The formula consists
of the number of chromosomes, the complement of sex
chromosomes, any autosomes that are deficient
or in excess, and a description of any rearranged
chromosomes. A normal female is 46,XX and a normal male is 46,XY.
A female with trisomy 21 is 47,XX,+21.
A male with Klinefelter syndrome is
47,XXY. A male embryo that is monosomic for chromosome 5 is 45,XY,-5.
The description of rearranged chromosomes is more complex.

Klinefelter syndrome
A condition in males due to having two X chromosomes plus one Y chromosome.
The karyotype formula is 47,XXY.
Affected persons are tall, somewhat eunuchoid in appearance, and sterile.
They often have some breast development (gynecomastia). Intelligence
is normal. The cause is nondisjunction
involving sex chromosomes, which can lead
either to an ovum with two X chromosomes or a sperm with one X and one
Y chromosome. There is increased risk with advanced age of the mother,
consistent with many of the cases resulting from maternal nondisjunction.

knockout mouse A mouse in which a specific gene has been inactivated. This is accomplished by introducing a nonfunctional gene by homologous recombination into embryonic stem cells in culture, injecting the modified stem cells into an early mouse embryo (blastocyst), and implanting the resultant chimeric embryo into a foster mother. Chimeric offspring produce nonchimeric gametes, some of which have the inactivated target gene. These gametes produce heterozygous mice, which can be interbred to produce homozygous mice. Knockout mice are useful in studying the function of specific genes by observing the effect on the phenotype when no functional form of the gene is present.

lactase persistence The persistence beyond infancy of the enzyme lactase, necessary for the breakdown of lactose, the sugar in milk. The young of mammals, including humans, produce this enzyme through the nursing period. After that, its production diminishes in most humans and in other mammals. Persistence of lactase production is a dominant monofactorialpolymorphic trait in all populations. Persons who continue to produce lactase can consume fresh milk with no problem. Persons without lactase often have difficulty with milk products because of the high level of lactose in the gut and the joy with which bacteria greet this condition. Diarrhea and other intestinal upsets follow. In Asian populations, the frequency of the persistent phenotype is very low; in Scandinavians, it is very high. Most of the world is inbetween. Additional information is available in OMIM.

lactose The sugar that occurs in milk. Lactose is a disaccharide with one molecule each of glucose and galactose joined by a covalent bond. When consumed, it is broken down by the enzyme lactase into glucose and galactose, which are efficiently absorbed in the intestine.
Many persons do not have this enzyme as adults and do not tolerate lactose in the diet. (See lactase persistence.)

lemur An early primate, represented today by a number of species on the island of Malagasy. Lemurs are arboreal and largely nocturnal. The line that gave rise to lemurs and lorises split off from the line leading to humans some 55 million years ago.

Lesch-Nyhan syndrome An X-linked recessive disorder that occurs as a result of lack of the enzyme hypoxanthine phosphoriboxyl transferase. Affected individuals are males who are mentally retarded. In addition they are prone to self mutilation,
biting off lips, fingers, etc. Additional information is available in OMIM.

leukocyte [Greek leukos white + kytos cell] A white blood cell. There are several types of leukocytes, all of which are involved in immunity.

light chain One of the two types of polypeptide chains found in antibodies. See antibody for more details.

linkage Refers to genetic markers that
are in the same linkage group.

linkage group A group of genetic
markers that have been shown by genetic mapping to be close to each other on the same chromosome.

Linnaeus The Latinized name of Carl von Linné (1707-1778), a Swedish botanist who established the binomial system of classification of organisms.

local population A small population, typically a population that is reproductively isolated, that is genetically distinct. Roughly synonymous with local race.

local race A small population that is genetically distinct from surrounding populations.

locus [Plural loci.] The location
of a gene or other genetic variation or landmark.

loris Primitive primates that share many features with their close relatives, the lemurs. The two groups separated from each other some 15 million years ago.

low-density lipoprotein (LDL)
A complex of cholesterol and proteins that occurs
in plasma. In this form, cholesterol is delivered to various tissues
but primarily the liver, where it is taken into the cell. The cholesterol
released in the cell regulates further synthesis of cholesterol through
a negative feedback system. High levels of LDL in the blood are associated
with high risk of heart disease.

lymphatic system [Greek lympha water] The system of vessels that drain excess fluid (lymph) from tissues, through collecting centers (lymph nodes), and eventually back into the blood stream. Lymph nodes are important in immunity as collecting sites for bacteria and viruses and as the sites for production of lymphocytes.

lymphocyte [Latin lympha water + -cyte.] A type of white blood cell. Lymphocytes are divided into B-cells and T-cells, both critical to immune responsiveness. Each of these types has subtypes with specific roles in immune response. Lymphocytes can be cultured in the laboratory and are the most common cell type used in characterization of chromosomes (karyotyping).

Lyon hypothesis The
hypothesis, first clearly stated by Mary F. Lyon, that only one X chromosome
is active in mammalian cells with two or more X chromosomes. See X-chromosome
inactivation.

lyse [Greek lysis dissolution] Disruption of a cell membrane, destroying the integrity of the cell structure.

lysosome [Greek lysis dissolution
+ soma body] An organelle whose
function is the break down of various substances in the cytoplasm.

macrophage A white
blood cell of the granulocyte series that consumes foreign substances, especially those that have been marked by binding of antibodies. Macrophages are the scavengers of our bodies, cleaning up the unwanted debris.

major histocompatibility complex (MHC) The highly polymorphic complex of tissue antigens coded by a cluster of closely linked genes on human chromosome 6. These antigens are primarily responsible for rejection of tissue and organ transplants that occurs when
the recipient generates an immune response against "foreign" antigens. (The prefix histo- refers to tissue.) There are additional, minor histocompatibility loci, about which little is known since they do not usually cause problems. The number of MHC loci and the high degree of polymorphism at each means that the likelihood of a complete match of antigens between two persons selected at random is vanishingly small. Yet that is an important consideration in organ transplants. A mismatched transplant is likely to be rejected because
of an immune response on the part of the recipient. Because of the proximity of the MHC loci to each other, crossing over within the complex occurs rarely, and the transmission of the allelic combinations (haplotypes) can be treated as a simple Mendelian system. Parental crosses would typically be ab × cd, potentially producing children of four haplotype combinations: ac, ad, bc, and bd. Thus a pair of siblings would have a 25% chance of matching, a prospect that is relevant to kidney and bone marrow transplants but not to most other organs. The availability of drugs that suppress the immune system has made some degree of mismatch feasible, and partially incompatible organ transplants are now done frequently.

malaria A disease due to infections by certain species of the genus Plasmodium. Symptoms include high fever and shaking chills, anemia, and enlarged spleen. Severe forms can lead to death. The infection is transmitted by Anopheles mosquitoes. Falciparum malaria, caused by P. falciparum, is the most severe form and occurs widely in tropical regions. Vivax malaria is caused by P. vivax and is less severe than falciparum malaria. It occurs in both tropical and temperate zones. Other species of Plasmodium can also cause malaria but are much less widespread. Malaria is thought to have been an important selective agent in human evolution.

Marfan syndrome A dominantly
inherited disorder of the fibrillin-1 protein, which occurs in connective
tissue. Affected persons are tall, with frequent spinal curvature (scoliosis)
and developmental abnormalities of eyes and heart. The fibrillin-1 gene
is located on chromosome 15 at 15q21.1. Additional information is in OMIM.

maternal inheritance
Transmission of an inherited trait only from females and to all offspring
of a female. Maternally inherited traits are due to variations in DNA of
mitochondria
(and to chloroplasts in plants). These cytoplasmic organelles are transmitted
to the zygote only via the maternal gamete.

meiosis [Greek meiosis diminution.]
The formation of haploid germ cells from a diploid parent cell. Meiosis
involves two steps. In the first, called meiosis
I or MI, paired homologous chromosomes separate, reducing the chromosome
complement in the daughter cells to haploid. Each of the chromosomes consists
of two sister chromatids with an undivided centromere. An additional division
then occurs (meiosis
II or MII), which is comparable to mitosis in that the centromeres
divide and sister chromosomes go to different daughter cells.

meiosis I The first of two
divisions in meiosis, often abbreviated MI. In prophase (prophase I), homologous
chromosomes pair, and crossing
over occurs. At metaphase (metaphase I), the paired homologues align
to form the metaphase
plate. At anaphase (anaphase I), the members of a homologous pair separate
and move to opposite poles. The two daughter cells thus have a haploid
set of chromosomes, each of which has two chromatids and an undivided centromere.
MI begins with one diploid cell and ends with two haploid cells.

meiosis II The second of
two divisions in meiosis, often abbreviated MII. It is similar in many
respects to mitosis.
After the alignment of the chromosomes at metaphase (metaphase II), the
centromeres divide, and the new sister chromosomes move to opposite poles
during anaphase (anaphase II). MII begins with two haploid cells and ends
with four haploid cells.

memory cell A B- or T-lymphocyte that is long lived and that can produce specific antibodies or T-cell receptors. These cells arise after antigenic stimulation and serve as the "historians" of the immune system, providing a quick start in the event of subsequent exposure of the organism to the same antigen.

-mere [Greek meros part.]
A common suffix that means part, as in centromere.

messenger RNA (mRNA)
The form of RNA that is generated by transcription
of a gene in the nucleus and that then moves to the cytoplasm where it
binds to ribosomes for assembly of a protein.
Often the primary transcript must be
processed by splicing out the introns and modifying
both the 5' and 3' regions in order to produce functional mRNA

meta- [Greek meta after, beyond.]
A prefix that is often used to mean outside of or parallel to.
In genetics, it typically has a meaning equivalent to middle.

metabolic error A defect
in an enzyme that catalyzes
a metabolic step, causing the metabolic conversion
not to occur. The common cause of metabolic errors is a defective gene
that codes for a nonfunctional or missing enzyme.

metabolic pathway
A sequence of consecutive metabolic steps where one of the products of one reaction becomes a substrate for the next.

metabolism A general term
referring to the chemical conversions that occur in an organism. Each conversion
can be thought of as a step, and the vast majority of steps are catalyzed
by enzymes. Enzymes, which are proteins,
are coded by genes. Therefore, each metabolic step
is catalyzed by an enzyme that consists of one or more different polypeptides.
Each polypeptide in the enzyme corresponds to a unique gene.

metacentric Descriptive
of a chromosome in which the centromere
is located approximately in the middle, creating arms of similar, though
not usually identical, length.

metaphase The phase of mitosis
or meiosis
in which chromosomes are maximally condensed and are aligned in a plane
between the poles of the spindle.
Metaphase marks the end of prophase.
It is followed by anaphase.

metaphase plate The
array of chromosomes in a plane that characterizes metaphase. The metaphase
plate forms between the poles of the spindle
and perpendicular to the spindle axis.

metric system The measure
of length used in science and most parts of the civilized world other than
the U.S. One meter (m) = 39.37 inches. One centimeter (cm) = .01 meters
= 2.54 inches. One millimeter (mm) = .001 meters. One micrometer = 10–6
meters. One nanometer (nm) = 10–9 meters.

microtubule A structural
element that participates in many cell functions. Microtubules consist
of protein subunits that associate under certain cell conditions and that
dissociate under others. This allows microtubules to form and disappear
rapidly. One of the numerous functions of microtubules is formation of
the spindle
during mitosis and meiosis. During metaphase, some of the microtubules
attach to the centromeric
regions of chromosomes, and the chromosomes are then pulled along the microtubules
to the poles of the spindle during anaphase.

mitochondrion [plural
mitochondria] An organelle in the cytoplasm
of eukaryotic cells that uses oxygen to oxidize simple organic substances,
using the released energy to form ATP,
the "energy currency" of biological systems. Mitochondria are unusual in
that they contain small amounts of DNA that code for some of the gene products
necessary for mitochondrial function. Many others are coded in the nucleus,
however. Mitochondria replicate by division. Each has multiple copies of
the DNA, and there are many mitochondria per cell, sometimes thousands.
As a result, when a cell divides and each daughter cell receives a portion
of the cytoplasm, there is a good supply of mitochondria in each. In sexual
reproduction in many organisms, including mammals, the fertilized egg receives
all its cytoplasm, including its mitochondria, from the ovum and none from
the sperm. Therefore, variations in mitochondrial DNA are maternally
inherited, i.e. a mother transmits the variation to all children, and
males never transmit the variation. A small number of human conditions
are due to mitochondrial variations and show maternal inheritance.

mitosis Refers to cell division
in which the two daughter cells each have a genetic makeup that is identical
to that of the parent cell.

MNSs blood groups An antigenic system expressed on the surface of human red blood cells. The antigenic variations were first detected with rabbit antibodies produced by immunization with human blood cells. Eventually, the responsible antigens were identified as glycophorin A (MN groups) and glycophorin B (Ss groups), both proteins having strong structural homology in the N-terminal region and coded by two closely linked genes on chromosome 4. The MNSs blood groups are universally polymorphic in populations around the world. The MN variations (glycophorin A) were among the very few genetic markers available prior to 1955, and they were extensively used in genetic and anthropological studies for that reason.

monoclonal Cells or individuals that are descended from a single cell. The meaning is the same as clonal, but the prefix emphasizes the single cell origin. The term is used especially with certain antibodies and with tumors.

monofactorial inheritance A trait whose variation is due to alleles at a single locus.

monohybrid cross A mating, especially in experimental genetics, between parental stocks that have different alleles
at one locus of interest. Other genetic differences between the parental stocks may
exist but are ignored.

monomorphic In genetics, a locus for which there is only one common allele. Common is defined arbitrarily as 1% or greater.

monosomy The condition in
a diploid organism of having only one of a particular
chromosome rather than the expected two homologous chromosomes. Monosomy
occurs as a result of nondisjunction or of
chromosome lag (failure of a chromosome to be incorporated into the daughter
cell complement). In humans, embryos that are monosomic for an autosome
do not survive. Females who have only one X chromosome have Turner
syndrome.

monozygotic The term applied
to twins who are derived from a single zygote.
They are genetically identical and are also called identical twins or MZ
twins. They arise when a very early embryo splits, and each of the two
parts develops into a complete embryo. MZ twins do not appear to cluster
in families. Therefore the tendency for MZ twinning does not appear to
be inherited.

mosaic An individual, some of
whose tissues differ from the remainder by a single gene or chromosome
mutation. This arises when the mutation or
nondisjunction occurs in a somatic
cell during embryonic development. Contrast with chimera.
Mosaicism in gene expression can also result from X-chromosome
inactivation, in which genes on only one of the two chromosomes is
expressed.

Mullerian duct In female embryos,
the Mullerian ducts give rise to the fallopian
tubes, the uterus, and the upper third of the vagina. In male embryos,
development of these structures is prevented by anti-Mullerian
hormone.

multifactorial inheritance A trait whose variation
is attributed to combinations of alleles at multiple loci
and that may also be influenced by environmental factors.

multiple alleles The existence
of two or more alleles
at a particular locus. Some loci have only one common allele and are called
monomorphic.
Others have two or more common alleles and are polymorphic.
Every gene locus has the potential to mutate
to a vast number of different forms. For certain loci that have been extensively
examined, such as the globin
loci of hemoglobin, hundreds of variant alleles have been recorded, most
of which are rare. The phenotypic effects of many alleles are likely to
be indistinguishable. For example, many will cause the protein product
of the locus to be completely inactive, leading to the same phenotype.
In other instances, subtle phenotypic differences may be associated with
different alleles.

multiple polyposis of the colon Several dominantly inherited conditions in which there are many, sometimes hundreds, of benign tumors (polyps) in the colon and intestine. The probability is high that one or more of the polyps will become malignant. Although the cancer per se is not inherited, pedigrees in which a multiple polyposis allele is segregating show typical Mendelian dominant patterns for colon cancer.

muscular dystrophy Deterioration
of muscle functions. The most common form is due to mutations at the dystrophin
locus on Xp. Some mutations produce severe effects (Duchenne muscular dystrophy);
others are milder (Becker muscular dystrophy). Both, however, are due to
mutations, usually deletions,
in the dystrophin gene. Duchenne MD typically appears in young boys, with
progressive deterioration and death in the teens. Duchenne and Becker MD
are classic examples of X-linked recessive inheritance. Additional information
and links are at OMIM.

mutation A heritable change
in DNA structure. Mutations may modify the coding region of a gene,
the regulatory region, or both; or they may be limited to intergenic regions.
They may be as small as single nucleotide changes or as large as deletions
of blocks of genes.

mutation rate The rate
at which mutations occur, either spontaneously or induced by exposure to
external agents. Mutation rates can be expressed in various ways,
depending on the means of observation, the tissue, and the use to be made
of them. Most commonly in human genetics, the mutation rate µ =
mutations per locus per gamete (or per generation, which is equivalent).
Mutation rates based on alteration of phenotype do not include those changes
in DNA that do not affect the phenotype. Phenotypic changes also can occur
as a results of mutations in noncoding regulatory regions of genes.
Therefore every mutation rate should include the endpoint used for detection.
Typical mutation rates for rare dominantly inherited diseases are in the
range 104 to 106, with an average about 105 mutations per gamete per
locus. This means that a particular sperm or ovum has
an average chance of 1 per 100,000 of having a detectable mutation
at the locus in question. Mutation rates can differ between males
and females. The highet mutation rate known is for the Duchenne muscular
dystrophy (DMD) geneca. 1 per 10,000 gametes. This is very likely
due to the very large size of the DMD gene2.5 million nucleotide pairsthat
presents a very large target for mutation. The mutation rates that
have been measured may be unrepresentative of all genes, since genes with
very low mutation rates are less likely to be known and selected for study.
A figure of 106 is perhaps more representative. Mutation rates for
single nucleotide changes, irrespective of phenotypic effect, have been
estimated about 108/nucleotide/gamete.

N-terminus The end of a
polypeptide chain at which is found the free
amino group. In assembly of polypeptide chains
in the cell, the process starts with the N-terminal amino acid. Its carboxyl
group is joined by a peptide bond to the
amino group of a second amino acid, and so on. The amino group on the first
amino acid points away from the growing end of the polypeptide chain and
never forms a peptide bond.

neoteny [Greek neos new + teinein to extend.] The retention in adults of childhood characteristics.

neural tube defect A congenital defect of the spine in which the embryonic structure known as the neural tube fails to close properly. This may result in bulging out of the spinal cord (spina bifida) and in other abnormalities such as anencephaly.

neutron A subatomic particle
that has the mass of a proton but that is electrically
neutral. Variation in the number of neutrons in an atomic
nucleus changes the mass of the atom but not the chemical properties.

New World monkeys Monkeys of the superfamily Ceboidea, found at present in South and Central America. Generally rather small, many have developed prehensile tails that can be used to hang from branches or grasping objects. The Ceboidea are thought to have diverged from the primate lineage leading to humans earlier than the Old World monkeys.

nondisjunction The failure
of chromosomes to separate properly in mitosis or
meiosis. Rather than the two homologous chromosomes
moving to opposite poles of the spindle, both move
to the same pole. This causes one daughter cell to have an extra
chromosome and the other to have a deficiency. Ordinarily, a single
chromosome pair is involved in nondisjunction, but rarely two or more be
involved. Meiotic nondisjunction is responsible for several instances
of chromosome imbalance, involving especially chromosomes 13, 18, and 21
and the sex chromosomes. In fact, nondisjunction
occurs with all chromosomes, but only those listed are observed in newborns.
The remainder routinely abort spontaneously. Meiotic nondisjunction
occurs primarily in meiosis I of females, and
the risk increases strongly with age.

nonrecombinant The presence in a
gamete of alleles that were received by the producer of the gamete from
the same parent.

nuclear envelope Sometimes called
the nuclear membrane, it is actually a double membrane that encloses the
nucleus
of eukaryotic cells. The nuclear envelope has many nuclear pores
that regulate the passage of substances between the nucleus and cytoplasm.

nucleic acid Complex molecules
that are formed by assembly of nucleotides into
a linear polymer. Two types are found in biological
systems: ribonucleic acid (RNA), in which
the building blocks are ribonucleotides,
and deoxyribonucleic acid (DNA), in
which the building blocks are deoxyribonucleotides.
DNA is found almost exclusively in nuclei and is the primary repository
of genetic information. RNA is found both in cytoplasm and nuclei
and is a secondary repository of genetic information (with the exception
of some viruses, in which it is primary). Nucleic acids can be described
as informational molecules because of their ability to store information
in the form of different nucleotide sequences.

nucleolus [Plural nucleoli] Darkly-staining
bodies seen in nuclei. Nucleoli are the sites of
ribosomal RNA synthesis and ribosome
assembly prior to movement of the ribosomes to the cytoplasm.

nucleosome Nuclear structures
composed of histones around which DNA
is wrapped.

nucleotide substitution
The replacement of a nucleotide (A, G, C, or T) with any of the other three
nucleotides at a particular position in DNA. This is a common type
of mutation. If it occurs within the coding
region of a gene, the codon will change, producing
either a synonymous mutation or a missense
mutation.

nucleus [plural nuclei] An organelle
that occurs within eukaryotic cells. It contains
the chromosomes and genes and, accordingly, is the master control center
of the cell. It is encased in a double-membrane nuclear envelope that regulates
the passage of materials between the nucleus and cytoplasm.

nullisomy Absence of any
copies of a chromosome.

Old World monkeys Monkeys of the superfamily Cercopithecoidea, found in Asia and Africa. Prominent members are the macaques and the baboons. Many are arboreal, but some are entirely terrestrial. This diverse group of monkeys is thought to have diverged from the hominoid line after the New World monkeys.

oncogene
A gene whose overexpression is associated with cancer.
Overexpression occurs by any of several mechanisms. Oncogenes were first
identified by their presence in certain viruses. When
it was recognized that the virus originally got its copy of the oncogene
from the host and that the gene was normal in the host cell, the two forms
of the oncogene were designated v-oncogene (viral-oncogene)
and c-oncogene (cellular-oncogene, also known as proto-oncogene).
The v-oncogene is under regulation of the viral promoter,
and transcription occurs along with viral genes.
Dozens of oncogenes have been identified, and they normally function in
a number of different ways in cells. The common element is that overexpression
interferes with the normal regulation of cell growth and leads to inappropriate
growth and division.

oöcyte A germ cell in the ovary that
has initiated meiosis
but not completed it. A cell that is in meiosis I is called a primary
oöcyte; one that has completed meiosis I is a secondary oöcyte.
In mammals, the ovum
is actually a secondary oöcyte that completes meiosis only if fertilized.

orangutan One of the great apes, assigned to the genus Pongo, found today in Borneo and Sumatra. In spite of their size, orangutans are primarily arboreal and use brachiation as a means of locomotion. The orangutan evolutionary lineage separated from the gorilla/chimpanzee/human lineage some 15 million years ago, but there are still marked similarities between orangutan and human karyotypes.

organic moleculeMolecules
that include carbon in their composition. Such
molecules were once thought to form only in organisms; thus the name.
Proteins, carbohydrates, nucleic acids, fats, etc. are all organic molecules.

osteogenesis imperfecta Any of several inherited disorders of collagen structure. A conspicuous feature is brittle bones, with multiple fractures following mild trauma. Access to entries on osteogenesis imperfecta can be found in OMIM.

ovarian follicle A structure in
an ovary that contains a single oöcyte.
Immature follicles contain oöcytes that are arrested in late prophase
I. Once each month, a follicle matures and releases an ovum, which
is a secondary oöcyte.

ovarian teratoma [Greek teratos
monster + -oma tumor.] A tumor that forms in ovaries and that is
comprised of various types of embryonal tissues. Genetic analysis indicates
them to be derived from maternal germ cells through several mechanisms.
They are diploid, but many are homozygous
for loci near the centromere. This could occur
if the chromosomes in a secondary oöcyte divided
without cytokinesis to form a diploid cell.
Without a male contribution, such a cell does not develop normally, presumably
because of parental imprinting of genes.

ovary The female gonad.
The female germ cells are in the ovary and initiate meiosis
there. The ovary also secretes estrogens, promoting
the development of secondary sexual characteristics.

ovum An egg. In mammals, the ovum is a secondary
oöcyte.
If fertilized, the nucleus of the oöcyte completes meiosis II, and
the resulting haploid nucleus fuses with the male pronucleus
introduced by the sperm.

oxygen [Symbol O; atomic
number = 8; atomic mass = 15.999.]
A very important element for biological systems
and for other processes. Many substances combine with oxygen, either
directly or indirectly, releasing energy that can be used for other purposes.
In many organisms, including all eukaryotes, this
process of oxidation causes energy to be transferred to ATP,
which then serves as an energy source for many other processes. Oxygen
is an important component of a very large number of biological molecules.

P, F1, F2
Symbols used in experimental genetics to indicate the parental generation
in a cross between two stocks, the offspring of that initial cross (F1,
first filial generation), and the offspring produced by crossing the F1
individuals with each other (F2, second filial generation.).

p,q The chromosome
arms, defined by the position of the centromere,
typically are unequal in length. The short arm is designated p (petite),
and the long arm is q (which follows p in the alphabet).
For example, a gene located on 6q would be on the long arm of chromosome
6.

palindrome A sentence or phrase that reads the same backward or forward, e.g. "Madam, I'm Adam." In molecular biology, palindromes are complementary single-strand DNA sequences that are identical. For example, the sequence 5'-AGCT-3' would have as a complementary sequence 3'-TCGA-5', which is identical, though the two strands would pair in an antiparallel manner.

pangenesis The theory that all parts
of an organism contribute to the information in a germ cell by means of
particles called gemmules. This idea, formulated by Charles Darwin,
is similar to theories of the ancient Greek philosophers. It is now known
to be completely false.

parthenogenesis [Greek parthenos
virgin + genesis production.] Development of an ovum
without fertilization by a sperm. In some species,
parthenogenesis occurs by mechanical or chemical stimulation of the ova.
The chromosome set may be doubled to produce a diploid
embryo. Rumors to the contrary notwithstanding, there is no documented
case of parthenogenesis in humans resulting in a live birth. Such an individual
would, of course, be female in the absence of a Y
chromosome. See, however, ovarian teratoma.

passive immunityImmunity achieved by introduction of antibodies from another immune person rather than by active immunity. A common example are newborn children, who have antibodies from the maternal circulation. Injections of pooled gamma-globulin after exposure to an infectious agent is another example, based on the assumption/demonstration that the persons who contribute plasma to such a pool are likely to include some who have antibodies in their blood because of prior infection with the agent. Antibodies have an average life of only about three months, during which time they help protect the recipient. After that, there is no residual immunity.

pedigree analysis Examination
of pedigrees, especially human pedigrees, to confirm or disprove that a
particular trait occurs in families according to one of the patterns of
transmission predicted by Mendelian theory. Pedigree analysis is especially
useful in testing rare autosomal dominant traits and X-linked traits. It
is not useful ordinarily in testing rare, apparently autosomal recessive
traits, since affected persons would occur only in one sibship.

pedigree chart A graphical representation
of a family, showing the relationships among family members and the phenotypes
and genotypes of interest for persons in the family.

penetrance The likelihood that a particular
genotype
will be expressed in the phenotype.
A penetrance of 100% means that the associated phenotype always occurs
when the corresponding genotype is present.

phenocopy An environmentally caused phenotype
that mimics a genetic trait. Example: Phocomelia is a condition that involves
major reduction of the limbs, such that hands and feet may be attached
directly to the shoulders and hips, respectively. It can be caused either
by homozygosity for an autosomal recessive gene (Roberts
syndrome) or by exposure to the drug thalidomide during embryonic development.

phenotype A term that refers to the expressed
traits of an organism, irrespective of whether or to what extent the traits
are the result of genotype
or environment.

phenotypic ratio The distribution
of phenotypes among the offspring of a specific genetic cross. The phenotypic
ratios may differ from genetic
ratios depending on the dominant/recessive relationships of the alleles
that are segregating.

phenylketonuria (PKU)
A recessive metabolic disorder in which the enzyme phenylalanine hydroxylase
(PAH) is missing. This enzyme catalyzes the conversion of the amino acid
phenylalanine to tyrosine. When PAH is missing, phenylalanine accummulates
to high levels in the blood. It and some of the other products to which
phenylalanine is converted interfere with other metabolic steps. The phenotype
includes mental retardation, hyperactivity, and reduced pigmentation. Reduced
phenylalanine in the diet of young affected children prevents development
of these characteristics. The gene for PAH is on chromosome 12. Additional
information is available in OMIM.

phosphoric acid A chemical
compound consisting of an atom of phosphorus, to which three hydroxyl
groups and one double-bond oxygen atom are attached. The hydrogen
atoms of the hydroxyl groups are highly likely to dissociate as hydrogen
ions, making phosphoric acid a strong acid. The negative phosphate
ion (PO4)3– occurs in biological systems associated
with various positively-charged cations. Phosphate can also form
covalent bonds between one or more of its hydroxyl groups and hydroxyl
groups on other molecules, splitting out water (H2O) in the
process. This occurs, for example, in nucleotides and in polynucleotide
chains of DNA and RNA. Regulation of the activities of many proteins
is by means of adding or removing phosphate.

phosphorus [Symbol P;
atomic number = 15; atomic mass = 30.974.] A critical element
in many biological processes. Phosphorus usually occurs in biological
molecules in combination with oxygen in the form of phosphate.

phylogeny [Greek phylon tribe + genesi origin.] The origins of the various groups of organisms; reconstruction of the evolutionary pathways that led to different organisms.

plasmid A DNA particle in some bacteria that has the ability to replicate with the bacterial cell but that is not part of the bacterial genome. Plasmids are important tools in genetic engineering, as they can be isolated, modified structurally, usually by insertion of genes or other DNA of interest, and inserted back into bacterial cells, where they replicate.

ploidy The ploidy of a cell refers to the
number of sets of chromosomes it contains. In
humans, a haploid cell has 23 chromosomes (22 autosomes
+ one sex chromosome). Diploid
cells have 46 chromosomes, triploid cells have
69, etc. The ploidy is frequently represented by multiples of n,
e.g. haploid cells have n chromosomes, diploid cells have 2n,
triploid cells have 3n.

point mutation A small
mutation, often equated to change in a single nucleotide. Also used,
especially historically, to refer to mutations in a single gene in contrast
to multigene deletions. Prehistorically, any mutation that could
not be observed by microscopic examination.

polar body At the completion of meiosis
I in an oöcyte, one of the haploid products is extruded from the
main body of the cell to form a polar body. It consists of little
more than the extruded nucleus and a bit of cytoplasm, surrounded by a
plasma membrane. If the ovum is fertilized and meiosis
II is completed, one of the meiotic products is again extruded to form
a second polar body. Polar bodies do not have a future.

polygenic A trait whose variation is
due to a combination of alleles
at multiple loci.

polymer A large molecule that
is produced by connecting subunits to form a chain. In homopolymers,
the subunits are identical, e.g. -A-A-A-A-. In heteropolymers,
two or more kinds of subunits are used, often in an alternating pattern,
e.g. -A-B-A-B-A-B-. These are examples of linear polymers,
since assembly occurs only in one dimension. Both DNA and RNA are
linear polymers of nucleotides and can be either homo- or heteropolymers.

polymerase chain reaction (PCR) A procedure for amplifying geometrically a particular segment of DNA. The principle depends on the requirement by DNA polymerase of a primer with a 3' end to which nucleotides can be added. Two such synthetic primers define a segment that is replicated in a thermal cycle of denaturation, reannealing (reformation of complementary primer-DNA structure), and replication. Each cycle, which takes 2-3 minutes, doubles the amount of DNA between the primer boundaries. Thirty cycles would thus yield 230 copies. PCR has made it possible to characterize extremely small amounts of DNA, such as that in a single sperm.

polymorphic In genetics, a locus
at which there are two or more common alleles. Common
is defined as having a frequency of 1% or greater.

polynucleotide A polymer
composed of nucleotides, either ribonucleotides
or deoxyribonucleotides, joined by covalent bonds.
Let B-S-P represent a single nucleotide. Both the sugar
(S) and phosphate (P) can form an additional
covalent bond. When this occurs, S of one nucleotide forms a bond
to P of the next; the S of the second nucleotide forms a bond to P of the
third nucleotide, etc. This generates a linear structure that can
be represented -S-P-S-P-S-P-, with the purine and pyrimidine bases attached
to the S groups and projecting out from the axis of the -S-P- chain.
Very large numbers of nucleotides can be assembled into a polynucleotide
chain. In the case of some human chromosomes, the DNA has tens of
millions of deoxyribonucleotides in single, monstrous polynucleotide chains.

preformation The archaic idea that
germ cells contain a completely formed individual. Some persons (the ovists)
thought that the individual (homunculus) is in
the ovum. Others (the spermists) believed it to be in the sperm.
Preformation does not provide for equal contributions from both parents.
It is the opposite of epigenesis.

preimplantation
embryo An embryo from the time of fertilization of the
ovum until the embryo implants into the uterine wall. Implantation occurs
approximately 7 days after fertilization. The embryo at that time is a blastocyst.

primer The general meaning of
primer is an object or act to get something started. As used in molecular
genetics, it is a short polynucleotide chain
that is necessary to initiate synthesis of a DNA strand by DNA
polymerase. It is necessary because DNA polymerase catalyzes
the addition of deoxyribonucleotides to the 3' end of a nucleotide that
is bound to the template to be copied. The 3' end
is provided by the primer.

proband The person whose phenotype led
to recognition that a particular trait is present in a family; the first
person in a family to be identified as having a trait and thereby calling
attention to the family. Other terms with identical meaning are index
case and proposit(us/a). The proband is usually indicated in
a pedigree chart by an arrow. In some statistical analyses, it is important
to know which family member is the proband.

prokaryote [Also spelled procaryote.]
A cell or organism without a nucleus. Examples include
bacteria. All prokaryotes are one-cell organisms. They contain DNA,
and the genes function much as in eukaryotes.
However, the DNA is not organized into eukaryote-like chromosomes
and is not contained within a membrane-bound organelle.

protein A biological linear
polymer whose building blocks are amino
acids. The amino acids are connected by a covalent
bond between the carboxyl group of one
and the amino group of the second. Such a dipeptide
can add another amino acid to form a tripeptide, and so on. A polypeptide
has larger numbers of amino acids in the peptide. A gene
functions by coding for the sequence of amino acids in a peptide. Thus
there is a direct relationship between the linear structure of DNA
and the linear structure of polypeptide chains. Twenty amino acids are
coded by DNA. Occasional modifications of one or more amino acids may occur
after incorporation into a protein. A polypeptide chain is rarely functional
as such. It must fold into a three-dimensioal form, the native form.
See primary structure, secondary
structure, and tertiary structure.

proton A subatomic particle
in the nuclei of atoms. A proton has
a single positive electrical charge.

proximal Refers to some event
that is nearer to the centromere than some specified marker
or landmark.

pseudoautosomal Genes that are
located in the small homologous segments at the tips of the short arms
of the X and Y chromosomes. These pseudoautosomal regions pair during meiosis
and undergo crossing
over. When considered independently of other loci on the X and Y chromosomes,
genes located in this region show transmission patterns characteristic
of autosomal
genes. However, they cosegregate with closely linked genes in the nonhomologous
regions of the X and Y chromosomes.

pseudohermaphrodite An individual
with ovaries or testes but with characteristics of the opposite sex. An
example is androgen insensitivity,
in which a mutation in the androgen receptor gene makes 46,XY embryos with
normal testes and testosterone production develop
into phenotypic females.

Punnett square A convenient diagrammatic
method for calculating probabilities of combinations of events, especially
useful in genetic crosses. Attributed to R. C. Punnett, an early geneticist.

quaternary code A code
in which there are four choices or letters. The binary code of computers,
for example, has two choices, either 1 or 0. In the DNA
code, there are four choices, G, A, C, and T. The number code commonly
in use has 10 choices and is a decimal code. The greater the number
of choices, the fewer digits required to specify a given number, word,
etc.

race A large population that is genetically distinct from other populations within the same species. The magnitude of the difference is not specified; hence, there can be quite varied opinions as to the existence of or number of races within a species.

radioactive isotope
An isotope that has an unstable nucleus and that
spontaneously disintegrates, releasing energy in the form of radiation.

random mating The selection of mates without regard to genotype. This is not as easy as it might seem. Mates are selected for a variety of attributes, many of which are influenced by heredity. Physical appearance is an obvious example. More subtle traits are intelligence and personality. In addition, we tend to select mates from our own social and ethnic groups, which may not be representative of the gene pool of the entire population. Random mating is not the same as haphazard mating. See assortative mating.

ras An oncogene
that was first identified in a rat sarcoma, hence the name. The normal function
of the ras protein is the receipt of signals from receptors in the plasma membrane and transmission to other cell components and thence to the nucleus. Normal ras proteins, after having been turned on by the signal, have a mechanism for turning themselves off. Mutant forms of ras cannot turn themselves off and continue to send signals to the nucleus to divide, thus contributing to the abnormal growth of cancer cells.

reading frame The reference
frame of three nucleotides with which messenger
RNA is "read" during translation. Translation
is initiated by the mRNA sequence AUG. That sets the reading frame,
and the following codons are established by taking three nucleotides at
a time.

receptor A protein
that binds to another substance (the ligand) in order to initiate
or modify some function. Many receptors are imbedded in the plasma
membrane and bind to ligands outside the cell. In some instances
this generates a signal at the cytoplasmic end of the receptor that modifies
cellular activities. An example is the insulin receptor, which responds
to the presence of insulin outside the cell. In other instances,
binding of the ligand to the receptor causes the complex to be taken into
the cell. The LDL (low-density lipoprotein)
receptor is an example. In the case of steroid receptors, the
receptor is located in the cytoplasm. Binding of estrogen or androgen
to their respective receptors activates the receptors to move into the
nucleus and modify the activities of specific target genes.

recessive Requiring two similar alleles
in order to be expressed in the phenotype. Such individuals are homozygous
for the recessive alleles.

reciprocal matings Matings in
which, on the one hand, a particular genotype is in the paternal stock,
and on the other hand, it is in the maternal stock. In Mendelian systems,
there should be no difference in the F1
and F2
generations from reciprocal matings. This applies to the great majority
of genes, but does not apply for genes on the X and Y chromosomes nor for
imprinted
genes.

recombination The combination in
a gamete of alleles that were received by the producer of the gamete from
different parents.

regression to the mean In
complex
inheritance, the mean values of offspring for a continuous trait tend
toward the average of the parental values. This has misled some persons
into thinking that phenotypic
variation in a population should decrease each generation. This ignores
the fact that the phenotypes of many offspring fall outside the parental
range. Overall, the phenotypic variation in a population remains constant
in succeeding generations, provided there is no change in environment or
genotypes
that modify the phenotypes.

repetitive DNA sequence A DNA sequence that is repeated a number of times, sometimes in tandem, sometimes scattered throughout the genome. Approximately 30% of the human genome is repetitive DNA, with several sequences repeated hundreds of thousands of times. No function has been established for these sequences. Some of the sequences that are repeated lesser numbers of times are very useful as genetic markers. See minisatellite, microsatellite.

reproductive isolation Lack of genetic exchange between populations. This can be due to geographic barriers, to behavioral barriers, or to reduced fitness of hybrids between the populations.

repulsion If two alleles of interest
are on different members of a pair of homologous chromosomes, they are
said to be in repulsion. If they are on the same chromosome, they are coupled.

restriction enzyme An enzyme that catalyzes the cleavage of DNA at a specific nucleotide sequence. More properly called a restriction endonuclease. The more useful restriction enzymes cut DNA at palindromic sites, creating two identical ends, often with identical single-strand tails that are complementary to each other. For example, the target sequence 5'-AGTACT-3' has an identical complementary sequence 3'-TCATGA-5'. If both strands are cut between A and G, both would have single-strand tails 3'-CATG-5'. These tails, being complementary, tend to stick together, generating a double strand of DNA with gaps between A and G, which can be religated by formation of covalent bonds. DNA fragments from different sources, if cut with the same restriction enzyme, can be joined together by means of their sticky tails and ligation.

restriction fragment A DNA fragment created by cleavage of a larger piece of DNA with a restriction enzyme. Very large pieces of DNA, such as the entire DNA in a genome, may be broken into many thousands of fragments. Each restriction enzyme generates its characteristic fragments because the DNA is cut only at target sites for that enzyme.

restriction fragment length polymorphism (RFLP)Polymorphic variations in size of a DNA restriction fragment, useful as a genetic marker. There are two mechanisms for the origin RFLP's: (1) A particular site on one chromosome will be cleaved by a restriction enzyme, whereas on another homologous chromosome it will not. A DNA probe that binds to either side of that site will indicate restriction fragments of different length, detectable in Southern blots. (2) The number of nucleotides between restriction sites varies. This is usually due to variations in numbers of repetitions of a nucleotide sequence. A Southern blot again will indicate different lengths for the restriction fragment. RFLP's are inherited as simple codominant Mendelian traits.

restriction site A DNA sequence that is the target site of a restriction enzyme. Some target sites consist of as few as four nucleotide pairs. There would be many such sites in a large piece of DNA. Other restriction enzymes have targets with as many as eight nucleotide pairs and would cut DNA at many fewer sites.

retinoblastoma [Gene symbol RB.] A malignant tumor of the retinoblast cells in the retina of the eyes of young children. The RB gene product is an important regulator of the G1 to S progression in the cell cycle. Cells that are homozygous for nonfunctional RB genes are unregulated. Persons who are heterozygous for RB are at high risk that at least one retinoblast cell will become homozygous through somatic mutation, thus generating a malignant tumor. Retinoblasts are incompletely differentiated embryonic cells present in young children. They disappear after several years. Retinoblastomas therefore occur only in young children, and the risk of retinoblastoma drops to near zero in older children. Additional information is available in OMIM.

retrovirus A very small virus that stores genetic information in the form of RNA, which is copied into DNA for replication in an infected cell. The DNA copies are catalyzed by RNA-dependent DNA polymerase, commonly called reverse transcriptase. The DNA copies of the retrovirus integrate readily into the DNA of host chromosomes, where RNA copies are made by the transcription machineray of the cell. The ability to integrate into host DNA makes them candidates for use in gene therapy. Many retroviruses have acquired a copy of a host gene, probably from host messenger RNA. If the products of such genes stimulate cell growth and division, the result may contribute to cancer. The extra gene would then be an oncogene. There are a number of retroviruses, of which the most important to human health is the human immunodeficiency virus.

reverse transcriptase The common term applied to RNA-dependent DNA polymerase. Making a DNA copy of RNA is the reverse of transcription. The enzyme is produced only by retroviruses, which use the cell machinery for replication. Since retroviruses store genetic information in the form of RNA rather than DNA, DNA copies must be made first in order for host DNA polymerase to act.

Rh (rhesus) blood groups A system of polymorphicantigens on human red blood cells. The antigens were originally discovered on the red cells of rhesus monkeys, hence the name rhesus blood groups, usually shortened to Rh. The antigen was also independently discovered on red cells of a newborn suffering from hemolytic disease of the newborn. Presence of the Rh antigen was shown to be a dominant trait, with Rh-negative persons homozygous for an allele associated with absence of the antigen. The genetics of the Rh system is now known to be more complicated, but for many purposes it can still be treated as a two-allele locus. People who are Rh-negative do not produce antibodies to Rh-positive antigens unless immunization has occured, either by blood transfusion of incompatible blood or by transfer of Rh-positive red cells from a fetus to an Rh-negative mother. Blood to be used for transfusion is routinely matched to the recipient for Rh. In reports of blood types, the Rh status is
indicated by the "positive" or "negative" that follows the ABO type. E.g. A person with type A, Rh-negative blood will commonly be described as type A, negative, which sounds to the novice as if A were negative. But you are no longer a novice!

RNA polymerase The enzyme that catalyzes assembly of an RNA strand,
using a DNA strand as the template. Strictly speaking, the full name should be DNA-dependent RNA polymerase, since some viruses can use an RNA template to make RNA.

schizophrenia A complex of psychotic disorders characterized by disturbance of thought, mood, and behavior. Delusions and hallucinations are frequent.

secondary structure In proteins, the structures that result when hydrogen bonds form between the hydrogen atom next to one peptide bond and the oxygen atom next to another. There are two stable structures that can form readily. One is a left-handed helix with hydrogen bonds formed between successive turns of the helix. The other is a "pleated sheet,"
in which the polypeptide chain folds back and forth in a plane to form parallel chains held together by hydrogen bonds between them. Both structures are common in native proteins.

segregation A term that
describes the separation of chromosomes and genes in meiosis.

segregation analysis
Analysis of the ratios of offspring from a particular parental cross to
test for conformity with Mendelian theory. Either genotypes
or phenotypes can be the object of segregation
analysis.

selection coefficient The loss of fitness of a particular genotype compared to the most fit genotype. This is expressed as s = 1  w, where w is the fitness, with values from 0 to 1, and s is the selection coefficient. For the most fit genotype, w = 1 and s = 0.

semen The suspension of spermatozoa
in secretions of the seminal vesicles, forming the ejaculate.

semiconservative replication
A form of replication characteristic of DNA.
When a double strand of DNA replicates, the
two strands separate, and each serves as a template
for the assembly of a new complementary strand.
The two daughter DNA molecules produced each consist of one old strand
and one new strand. The name semiconservative comes from the fact that
one old strand is completely conserved and the other strand is completely
new.

seminiferous tubules
Enclosed channels in the testes in which spermatozoa
are produced. The spermatozoa move from the seminiferous tubules into the
epididymis, where they are stored.

sense strand One of the
two strands of DNA in the coding region of a gene. One strand serves
as the template. The other strand, which
is complementary to the template strand, has
the same nucleotide sequence as the primary
transcript. The messenger RNA is
considered "sense." Therefore, the DNA strand with the same information
is also sense. This strand is also called the coding strand.

sex A means of genetic exchange,
creating cells or individuals with new combinations of alleles.
Sexual reproduction is in contrast to asexual reproduction, in which offspring
are genetically identical to the parental cell or individual, there being
only one parent rather than two.

sex chromatin A darkly-staining
body in the nuclei of cells from females.
This body, also called the Barr body after Murray Barr, one of the discoverers,
is produced by inactivation and condensation of one of the two X
chromosomes in females. See X-chromosome
inactivation.

sex chromosome A chromosome
that is involved in determination of sex. In mammals, females are produced
when the chromosome complement includes two X chromosomes. Males are produced
when there are one X chromosome and one Y chromosome. The X and Y chromosomes
are therefore sex chromosomes.

sex-influenced trait
A trait whose expression is different in males and females.

sex-limited trait
A trait whose expression is limited to one sex, either male or female.

sex-linked Any gene on the
X chromosome. The preferred term is X-linked,
in view of the presence of genes on the Y chromosome also.

sexual dimorphismPhenotypic variation between sexes. In many species,
there is relatively little difference in appearance of males and females.
In others, the differences can be striking. In some species of birds, males
have ornate plumage, whereas females are quite drab (by human standards).

sexual reproduction
Reproduction that is accompanied by exchange of genetic material. In mammals,
the haploidgametes
combine to form diploid
offspring that are different from either diploid parent. Sexual reproduction
is thought to be an advantage for a population because it generates new
combinations of alleles, some of which are associated with superior adaptation.
At the same time, some combinations would be less advantageous, and the
alleles responsible would be eliminated.

siamang One of the larger of the small apes, close relatives of gibbons.

sibship A set of siblings (brothers
and sisters).

sickle-cell anemia
An inherited disorder of hemoglobin
structure, common in persons of African origin. Persons homozygous for
the sickle-cell gene have red blood cells that form bizarre sickle shapes
when oxygen is low, as in peripheral tissues. Such cells clog the circulation
in blood capillaries, further reducing the oxygen and exacerbating the
problem. The sickled cells also are more likely to rupture, releasing hemoglobin
into the blood stream. Death usually occurs in the second decade. The genetic
change is in the gene that codes for the ß-globin subunit of hemoglobin.
The high early death rate among persons homozygous for the sickle-cell
gene appears to be offset in some populations by the greater resistance
of heterozygotes to falciparum malaria. See OMIM
for technical details and links to other sites.

sickle-cell hemoglobin (Hb S)
The inherited variation in the beta-subunit of hemoglobin (Hb) that causes
sickle-cell anemia in homozygotes. The change is in the sixth amino
acid from the N-terminus, which glutamic acid in the normal Hb A and valine
in Hb S. This causes the folding of the N-terminal region to change
when the oxygen is low, as in peripheral tissues. In high concentrations,
the modified folding in turn causes aggregation of the Hb molecules into
a crystal-like structure, which disrupts normal red cell morphology, forming
so-called sickle cells. Rupture of the red cells is a frequent
result.

sickle-cell trait
The condition of heterozygosity for the sickle-cell
gene. Some one-third of the hemoglobin
in the cells of heterozygotes is the variant Hb
S. In these concentrations, formation of sickle cells does not
occur in vivo although it can be induced in the laboratory.
Phenotypically, persons with sickle-cell trait are normal. The difference
between having a "trait" and having "anemia" is not obvious to persons
unversed in genetics and has caused much confusion and unnecessary concern.
Remember: sickle cell anemia = bad; sickle cell trait = not bad.

single nucleotide polymorphism (SNP) Variations among chromosomes at a single nucleotide position, e.g. A on one chromosome, G at the same site on another. These may occur in coding regions of a gene, but most are in the noncoding regions, which comprise most of the chromosomes. SNP's in restriction sites would also be detectable as RFLP's. However, PCR primers can be designed that will bind to one SNP form but not the other. SNP's are inherited as codominant traits and are especially useful as genetic markers because of their very low mutation rate.

somatic mutation A
mutation that occurs in somatic cells and that therefore cannot be transmitted
to offspring. Somatic mutations are important in genesis of cancer
and certain other disorders.

Southern blot A method, named after its inventor, E. M. Southern, for separating fragments of DNA and detecting the fragments that can bind a specific DNA probe. After gel electrophoresis, the gel is placed on wet filterpaper. The gel is covered by a nylon or nitrocellulose membrane, on top of which blotting materials (paper towels) are placed. The paper towels absorb liquid through the membrane, causing flow of liquid through the gel. DNA moves with the liquid but is stopped by the membrane, preserving the pattern of distribution of fragments originally in the gel. After the DNA on the membrane is denatured, the membrane is treated with a DNA probe to locate DNA bands that are complementary to the probe.

species The most basic unit of biological classification. Members of a species share many characteristics that distinguish them from other species. In particular, members of the same species can interbreed to produce fertile offspring; members of closely
related species can sometimes interbreed to produce offspring, which are typically sterile. [The word species is both singular and plural. The word specie refers to coins and not to a biological group.] See binomial nomenclature for additional levels of classification.

spermatid A male germ cell
that has completed meiosis
but that has not undergone the cellular conversions into a mature sperm
(spermiogenesis).

spermatocyte A male germ cell that has initiated spermatogenesis.

spermatogenesis The process of forming haploid germ cells in males.

spermatogonia Male germ cells that replicate by mitosis. Such cells are diploid and constitute the stem cell line in the testes that permits continual production of sperm
throughout the adult life of a male.

spermiogenesis The process
of forming mature sperm from the haploid products of spermatogenesis.

spina bifida A congenital condition in which the spinal cord is incompletely enclosed, resulting in extrusion from the spine.

spindle The structure formed
during nuclear division that participates in separation of chromosomes
into daughter cells. The spindle consists of microtubules
that radiate from two bodies (centrioles) that form the poles of the spindle.
At metaphase,
chromosomes are aligned in a plane between the poles and perpendicular
to the spindle axis.

spontaneous generation
The idea that living organisms can arise from nonliving matter. It is incorrect,
at least for modern organisms. The earliest forms of life must have originated
from nonliving systems, but that is quite a different story.

SRY The gene on the Y chromosome
of mammals that causes the gonads to develop into
testes. The gene symbol (SRY) comes from the
name sex-determing region Y. The presence or absence of the SRY
gene is the primary determinant of sexual development, although other genes
on the Y chromosome are also necessary for male fertility. Rare mutations
at other loci, including autosomal loci, can cause sex reversal, but allelic
variations at these loci do not contribute to normal sexual differentiation.
Additional information on SRY is available in OMIM.

stem cell A cell that replicates
mitotically
and that remains in a somewhat incompletely differentiated
state. Stem cells serve as a source of cells that have the potential to
differentiate but that have less or no potential to divide. Examples: bone
marrow cells that can differentiate into precursors of red and white blood
cells; spermatogonia
in the testes that produce a continual supply of cells that differentiate
into spermatozoa.

steroid Any of a class of chemical
compounds that have in common the steroid structure, a complex four-ring
structure. Cholesterol is a steroid and is the starting point for biosynthesis
of other important steroids, such as the adrenal hormones and the sex hormones
(androgens, estrogens,
and progesterone). Steroids are very hydrophobic
and can pass readily through plasma membranes into cytoplasm. Their function
as hormones is mediated by specific protein receptors in the cytoplasm,
which form complexes that then enter the nucleus and regulate the activity
of various genes.

stop codon A codon
that terminates translation rather than adding
an amino acid. Three of the 64 codons are
stop codons; the remainder code for amino acids.

structural protein
A protein that acts to stabilize the architecture of a cell, its interior
components, or multicellular arrays. Examples include spectrin,
on the interior of red blood cell plasma membranes, tubulin, in the microtubules
of cytoplasm, and collagen and fibrillin,
extracellular proteins that cause cells to adhere to each other.

substrate The substance
on which an enzyme acts. Often the product
of one enzymatic reaction becomes the substrate for another.

sugar Any of a group of chemical
structures characterized by chains of three to seven carbon
atoms, to most of which are attached one hydrogen
atom and one hydroxyl group. Because
of the multiple hydroxyl groups, sugars are very hydrophilic
and therefore soluble in water. The technical term for sugars is
saccharides. Glucose is a common monosaccharide important
in all life forms. It is a hexose, meaning that there are
six carbons in the chain. Other hexoses are fructose and galactose,
which differ from glucose in the three-dimensional arrangement of the H
and OH groups. Disaccharides are composed of two sugars connected
by a covalent bond. Examples are sucrose,
which is a combination of glucose and fructose, and lactose, which is a
combination of glucose and galactose. Pentoses (five-carbon sugars)
that are important players in biology are ribose,
which occurs in the nucleotides of RNA,
and deoxyribose, which occurs in the nucleotides
of DNA. Starch, glycogen, and
cellulose are large polymers of glucose, the first two serving as energy
stores in plants and animals, respectively. Sugars, starches, and
glycogen are carbohydrates.

synapsis [Greek synapsis
connection.] The pairing of homologous chromosomes during prophase I of
meiosis.
The pairing is highly specific, point-by-point matching. During this pairing,
crossing
over between nonsister chromatids occurs, generating new chromosomal
combinations of alleles.

T-cell receptor The receptor on the surface of T-lymphocytes responsible for binding to specific antigens.

T-lymphocyte One of the two major types of lymphocytes, responsible for cellular immunity. T-cells are so-named because they mature in the thymus gland. There are two major types of T-cells: helper T-cells and cytotoxic (killer) T-cells. Cytotoxic T-cells attack cells that have foreign antigens on their surfaces and destroy (lyse) them. Helper T-cells are necessary in the action of B-cells in producing antibodies and cytotoxic T-cells in killing target cells. The interactions among these various types of lymphocytes is complex and depends both on direct contact and on chemical messages. T-cells also generate a small group of memory cells that create a rapid response in the event of a second exposure to the specific antigen.

tarsier A small primate that occurs today only in parts of Southeast Asia. The tarsier is thought to be somewhat between other prosimians and monkeys in the development of higher primate characteristics. It is nocturnal, with large eyes facing forward, providing good stereoscopic vision in dim light.

Tay-Sachs disease
An autosomal recessive disorder involving deterioration of the central
nervous system and death in young children. The gene that is responsible
codes for the alpha subunit of the enzyme hexosaminidase A. This enzyme
is in lysosomes and functions to breakdown certain complex molecules in
the brain called gangliosides. The disease is rare except among Ashkenazic
Jews, in whom the incidence is ca. 1 per 3600 births. Additional information
can be found in OMIM.

telo- [Greek telos end.]
A common prefix to describe something at the end. Examples: telocentric,
telophase.

telocentric [Greek telos
end + centric.] A chromosome in which the centromere
is located at the end, producing a chromosome with only one arm. Humans
have no telocentric chromosomes. Mice, however, have all telocentric chromosomes.

telophase The final phase
of nuclear division. The chromosomes uncoil and become very extended, a
nuclear
envelope forms around them, and the new nucleus enters
interphase.

template A form or mold used
to create an object. In genetics, the term refers to a polynucleotide
strand that is used to assemble a complementary
strand. In DNA replication,
both strands serve as templates for the assembly of complementary strands.
In transcription, only one DNA strand serves
as a template for the RNA copy that is made.

teratogen [Greek teratos
monster + genesis production.] Any agent that interferes with normal
embryonic or fetaldevelopment.
The term usually is applied to chemical or physical agents, such as alcohol
or radiation. Variant genes can also be considered as teratogenic when
they interfere with development.

tertiary structure
The final level of folding of polypeptide chains
to form a functional, three-dimensional protein.

testis A male gonad; the primary
male sex organ. The testes, which are located in the scrotum, are the site
of production of spermatozoa and the primary site of production of testosterone,
the principal male hormone.

testosterone The principal
male hormone (androgen). Chemically, testosterone
is a steroid. It is made in and secreted by the
interstitial cells of the testes into
the blood circulation. Testosterone and estrogens
are also made in other tissues, especially the adrenal glands, in both
males and females, but the levels are typically much lower than in the
gonads.

tetramer A structure that
consists of four subunits. Examples: tetrapeptide, tetranucleotide,
or a protein complex composed of four proteins.

tetraploid A cell or organism
that has four sets of the basic haploid complement
of chromosomes. In the case of humans,
there would be 92 chromosomes (4 × 23).

thalassemia Any of a group
of anemias due to inherited defects in the quantity of hemoglobin
in the red blood cells.

totipotent The state of having full potential for development. The term is used to describe early embryonic cells that have not differentiated and thus have the potential to differentiate into any tissue.

Tourette syndrome Also known as Gilles de la Tourette syndrome, this disorder involves facial and vocal tics, jerky movements, echolalia (involuntary repeating of words said by others), and coprolalia (involuntary use of obscenities). See OMIM.

transcription Formation
of an RNA copy of a DNA
strand. Transcription is catalyzed by RNA polymerase,
in this case DNA-dependent RNA polymerase.

transcription factor
Any factor, usually protein or a protein complex, whose presence alters
the rate of transcription, either up or down. The factor may bind directly to DNA, usually
in the 5'-flanking region but sometimes more distant, or to other transcription
factors that bind DNA. Most transcription factors are quite specific
for their target genes.

transfer RNA (tRNA) A
small RNA whose function is to recognize the genetic
code and add the proper amino acid to the
nascent polypeptide chain during translation.
Each amino acid will bind to one or a few tRNAs. Each tRNA will bind
only to one amino acid. When the codon for a
particular tRNA shows up on the docking site of the ribosome,
the anticodon of that tRNA binds to the mRNA.
At the other end of the tRNA, the amino acid that is attached breaks the
bond to the tRNA and forms a peptide bond with the previous amino acid
added. The tRNA is then released and recycles.

transformation A general
term meaning to change from one form to another. It is often used
in genetics to refer to a change in phenotype
that results from, or possibly results from, a change in genotype. In the context of cancer, transformation refers to the change from regulated growth (normal) to unregulated growth (cancer).

translation The process
of transferring the information coded in messenger
RNA into the corresponding amino acid sequences of a polypeptide.
Translation occurs on ribosomes in the cytoplasm.
The process requires messenger RNA, aminoacyl
transfer RNAs, in addition to the very complex machinery of the ribosomes.

translocation Breaks
in each of two chromosomes or chromatids that exchange distal
segments before repair. The result is no loss of chromosomal material,
but genes that formerly were on one chromosome are exchanged with genes
on another chromosome. The karyotype
formula includes t(m;n) to indicate translocation between chromosomes
m and n. E.g. 46,XY,t(13;15) indicates that a translocation has occurred
between chromosomes 13 and 15.

transport protein
A protein whose function is to bind and transport
a substance from one part of the body to another. Examples are hemoglobin,
which transports oxygen from the lungs to the tissues, and transferrin,
which binds iron in the plasma and transports it to tissues, especially
liver.

tree shrew Small primates (prosimians) that live in trees in southeast Asia. Their diet is primarily insects. Although superficially they rather resemble squirrels, close anatomical analysis shows their clear relationship to primates. The ancestral stock of the primates is thought to have been much like the present-day tree shrews.

trinucleotide expansion
An event that occurs at rare loci that have repetitive sequences of three nucleotides, such as (CAG)n. If n exceeds a threshold value, which is different for each locus, it increases during transmission to offspring, sometimes to very large values. The mechanism is not fully understood, and the increase can be in males only, females only, or both,
depending on the locus. Below the threshold value, n is stable and does not increase during transmission. Typically, there are values of n above the threshold that have no phenotypic effect but are subject to expansion upon transmission. These ranges of n are described as premutations, whereas values of n that affect the phenotype are called full mutations. The greater the value of n within the premutation range, the more likely transmission is to cause a full mutation. This generates pedigrees in which anticipation is observed, i.e. the mutant phenotype appears at younger ages in succeeding generations and often with greater severity. The fragile-X
syndrome and Huntington disease are examples of genetic disorders that commonly result from trinucleotide expansions, though more conventional mutations are also known in the case of fragile-X syndrome.

triploid A cell or organism
that has three sets of the basic haploid complement
of chromosomes. In the case of humans,
there would be 69 chromosomes (3 × 23).

triplo-X syndrome
The presence in females of an extra X chromosome.
The karyotype formula is 47,XXX.
The extra X chromosome results from nondisjunction,
which could occur either in the mother or the father, though it appears
to be most often maternal. Imbalance of function of genes on the
X chromosome is largely prevented by X-chromosome
inactivation, and triplo-X females are essentially normal and fertile.
Contrary to expectation, there is no excess of 47,XXX or 47,XXY
syndromes among their offspring.

trisomy Having three copies
of a particular chromosome, i.e. the total number of chromosomes in a trisomic
cell is 47. Trisomy arises by means of nondisjunction.
Most human autosomal trisomies are aborted spontaneously.
However, trisomies 13, 18, and 21 (Down syndrome)
do occur among newborns. Trisomy should not be confused with triploidy,
which involves three complete sets of chromosomes, a total of 69 chromosomes.

trophoblast The spherical
shell of cells that comprise the blastocyst with
the exception of the few that are destined to form the inner
cell mass that develops into the embryo. The blastocyst cells invade
the walls of the uterus and participate in formation of the placenta. They
are genetically identical to the embryo, both being products of the same
zygote.

tumor progression The change in the characteristics of cancer from a slow-growing, therapy-sensitive form to a rapidly-growing, invasive, therapy-resistant form. Progression is thought to be primarily due to accumulation of mutations, each of which makes the tumor more aggressive.

tumor suppressor gene A gene that greatly increases risk of cancer when a cell becomes homozygous for nonfunctioning alleles. The presence of at least one functional allele therefore "suppresses" cancer, provided there are not other genetic changes in the cell that "cause" cancer. The retinoblastoma locus is a classic example of a tumor suppressor gene.

Turner syndrome Also
known as gonadal dysgenesis, Turner syndrome is due to a chromosome complement
of one X chromosome plus the normal autosomal complement. The karyotype
formula is 45,X (sometimes written 45,X0). Affected persons are
females, with short stature, typical facial appearance and webbed neck,
and fibrous streaks in place of ovaries. They have normal intelligence,
although there is a specific deficit in the spatial memory.

unbalanced translocation
A chromosome complement that contains a translocation with hemizygosity
for some chromosome segments.

unequal crossover
A crossover between mispaired nonsister
chromatids. The result is duplication
in one chromatid of the segment between the crossover points and deletion
of that segment in the other chromatid. Mispairing appears more likely
to occur if there is some similarity of DNA sequence
between the mispaired segments.

uniparental disomy
The condition in which the two members of a pair of homologous chromosomes
both come from the same parent. There are several possible mechanisms
for the origin of uniparental disomy: (1) joining of two gametes, one with
deficiency of a particular chromosome, the other with two copies of that
chromosome; (2) trisomy of a chromosome in the zygote, with early
loss of one chromosome to restore the euploid state; (3) monosomy for a
chromosome with duplication of that single chromosome to restore the diploid
state. See isodisomy and heterodisomy.

universal code Refers
to the fact that all forms of life use the same genetic
code.

vaccination The introduction of a bacterial or viral antigen into a person or other animal in order to stimulate immunity against those antigens. Typically, the antigen is either a preparation or extract of the killed bacteria or viruses, or it is an infection with live bacteria or viruses that have been modified so as not to cause disease.

valence The characteristic
number of chemical bonds that an atom can
form.

variable region The N-terminal regions of thee H and L chains of antibody molecules. This region is the part of the antibody that reacts with a specific antigen. The great variability reflects the antibody diversity that is necessary to combine with very diverse antigens.

virus A particle that contains
some of the genes required for self replication but that cannot function
outside a cell. Some viruses use DNA
as the genetic material; others use RNA.
Some destroy the cell that they infect; others integrate into the DNA of
the cell and replicate with the host DNA. Viruses are generally not considered
to be living, since they cannot function outside a cell. However, some
do seize control of cell machinery, subverting it to the virus's own purposes.

Wallace Alfred Russel Wallace (1823-1913), independently of Darwin, arrived at the idea of natural selection in 1858. Upon communicating these ideas to Darwin, both Wallace's and Darwin's were made public in 1858, and both are given credit for them, although Darwin's subsequent publications and presence in England rather than in the Southwest Pacific made him the more visible figure to the public.

Watson-Crick model of DNA
Although DNA was discovered in the
1870's by Friedrich Miescher, and the structure of polynucleotide
chains was established in the first half of the Twentieth Century,
this in itself was not sufficient to understand how DNA stored genetic
information, replicated it, and transferred it to the cytoplasm to provide
instructions for cell processes. In 1953, James D. Watson and Francis
Crick published two very short papers that proposed an additional level
of structure that proposed solutions to these problems. Their proposals
opened the age of molecular biology, an age that has yielded rich benefits
and that is expanding still. Their model of DNA consisted of two
polynucleotide chains oriented in opposite direction and held together
by hydrogen bonds. The model can be
visualized as a ladder, with the sugar-phosphate chains constituting the
outside supports and the bases pairing between the supports and forming
the rungs. Hydrogen bonds are weak and can form only if the orientation
of the participants is just right. In the case of DNA, "just right"
occurs when adenine and thymine
pair and when guanine and cytosine
pair. Thus and A on one ladder support must be paired with a T on
the other to form a rung, and G must be paired with C. A sequence
such as -G-T-T-C-A-C- on one half of the ladder would pair with -C-A-A-G-T-G-
on the other. These sequences are described as complementary,
much in the way that a film negative and a print made from it are complementary,
a dark spot on the film generating a light spot on the print and vice versa.
Because of the three-dimensional structure of the DNA components, the ladder
twists, generating a double helix (a helix
with two strands) that is right handed, i.e. when viewed down the axis
of the helix, the twist is clockwise as it moves away from you. The
two polynucleotide strands have "direction" due to asymmetry of the nucleotides.
The direction is indicated by labeling one end 5' and the other 3'.
(These numbers come from conventions that chemists have in labeling atoms
in a molecule. At one end, there is a hydroxyl group on the 5' carbon
of the deoxyribose, and at the other end, there is a hydroxyl group on
the 3' carbon of the deoxyribose. It will be sufficient for the moment
if you just remember that one end of a polynucleotide chain is 5' and the
other 3'.) The double helix will form only if the two strands are
antiparallel, i.e. if one is 5' to 3', the
other must be 3' to 5'. Watson and Crick proposed that information
is stored in DNA by the sequence of nucleotides, much as computers store
information as a string of 1's and 0's. They further proposed that
DNA replicates semiconservatively,
solving one of the large requirements of DNA structure.

wild-type A term used to
describe the common, usually normal alleles of a
gene.

X-chromosome inactivation
Inhibition of the activity of genes on all but one of the X chromosomes
in individuals with two or more X chromosomes. In 46,XX females, only one
of the two X chromosomes is fully active, the other being largely inactive.
Thus males with one X chromosome and females with two have the same effective
gene dosage for genes on the X chromosome. Inactivation occurs early in
embryonic development, the choice of which X chromosome to inactivate being
random in each cell. Once inactivated, a particular X chromosome remains
inactive throughout subsequent mitotic cell divisions.

X-linked Refers to any gene
on the X chromosome. Equivalent to sex-linked.

XX male A male with two X chromosomes
and no apparent Y chromosome. Most cases are due to translocation
of the SRY gene on the Y chromosome to an X chromosome.

XY female A female
with an X and a Y chromosome rather than two X chromosomes. Among the common
causes are mutations in the male-determining SRY gene
and mutations in the androgen receptor
gene.

XYY syndrome A condition
in which males have an extra Y chromosome, with karyotype formula 47,XYY.
The extra Y chromosome arises from nondisjunction in the father.
Affected males are slightly taller than other males of the same genetic
background, and some appear to be more impulsively aggressive and violent
than normal. They are of normal intelligence, and most do not have
major behavioral problems. Approximately one per thousand males is
47,XYY.

xeroderma pigmentosum
A group of recessive traits that result from defects in repair of certain DNA alterations.
Affected persons are unable to remove thymine and cytosine dimers, which form on exposure to ultraviolet light. This greatly increases the mutations in skin exposed to sunlight and leads
to multiple skin cancers.

Y-linked Refers to any gene on the Y chromosome.

yeast artificial chromosome (YAC) A "chromosome" that has been assembled by joining together DNA fragments that contain the elements of a chromosome, such as a centromere, telomeres, and replication origins, along with other DNA of interest. The YAC is then introduced into yeast cells, where it replicates as part of the normal replication of chromosomes. The advantage of YAC's is the very large pieces of DNA that can be inserted, much larger than in the case of bacterial vectors.

zinc finger One of several
motifs (DNA or protein sequences associated with certain functions) that
occur in proteins that bind directly to DNA. The name is derived
from the way the polypeptide chains fold, producing multiple loops joined
at their bases by an atom of zinc. When this motif is encountered
in a DNA sequence, the presumption is that the protein product functions
as a transcription factor.